Oral care compositions comprising phosphono-phosphate and anionic group containing polymers

ABSTRACT

Disclosed are oral care compositions of novel phosphono-phosphate and anionic group containing polymer compositions that have targeted uses with divalent cations and surfaces having divalent cations. These compounds can be used to deliver anionic character to surfaces such as calcium hydroxyapatite for use in oral care applications.

TECHNICAL FIELD OF THE INVENTION

The present invention relates to novel phosphono-phosphate and anionicgroup containing polymers. The present invention further relates tousing oral care compositions comprising the novel polymers.

BACKGROUND OF THE INVENTION

Chemical structures that interact with multivalent cations in solutionand with surfaces containing multivalent cations are useful formanipulation of these systems. Polyphosphates and pyrophosphate, forexample, have been used as builders in laundry and dish formulations tocontrol calcium and in drilling muds to prevent precipitation. They havealso been used in the oral care industry to help control tartar andreduce the thickness of the pellicle layer on teeth resulting in a slicktooth feel. Similarly, bisphosphonates, and hydroxy-bisphosphonates areactive components in osteoporosis pharmaceuticals due to their stronginteraction with calcium hydroxy apatite surfaces and are also used ascrystal growth inhibitors in dishwashing liquids and boiler systems.Each of these examples suffer from an inherent limitation.Polyphosphates are prone to degradation over time in aqueous solutionsat all pH's, ultimately leading to an increase in ortho phosphate insolution. Polyphosphate salts are also quite anionic in nature and arenot soluble in non-polar organic systems. Polyphosphates are, however,generally safe for consumption and find use in different food products.Bisphosphonates and hydroxy-bisphosphonates are, conversely, stable inwater for long periods of time, and can, depending upon the nature ofthe organic group attached to the bisphosphonate carbon, be made quitesoluble in organic systems. Bisphosphonates, however, are active to bonesurfaces and hence cannot be used in foods or other systems where theymight be accidently consumed due to their potent pharmacology. Polymerscontaining bisphosphonates of sufficient molecular weight to not passthrough the intestinal wall would likely not be bone active, however anylow molecular weight residual monomers or oligomers that could passthrough the intestinal wall make the use of such polymers prohibitive inpotential consumable contexts. In addition, since bisphosphonates do notbreak down readily, their activity can persist in the environment afteruse.

Therefore, a need still exists for a phosphate composition that does noteasily degrade and is safe for human consumption.

SUMMARY OF THE INVENTION

It has surprisingly been found that the phosphono-phosphate chemicalgroup ameliorates the concerns of polyphosphates and bisphosphonateswhile finding utility in similar systems. In particular, polymers thatcontain a phosphono-phosphate group, whether by incorporation of amonomer containing a phosphono-phosphate group, or by postpolymerization modification to add a phosphono-phosphate group, alongwith an anionic group can be used in numerous applications in whichpolyphosphates and bisphosphonate containing structures are used. Suchapplications generally include those in which binding interactions areinvolved with multivalent cations both in solution and on surfacescontaining bivalent cations. Phosphono-phosphate and anionic containingpolymers can also be used in applications where polyphosphates andbisphosphonate use is limited. The phosphono-phosphate group isconditionally stable and will only release phosphate under acidic orcatalyzed conditions. Hence the phosphono-phosphate group is more stablethan polyphosphate, but not as stable as bisphosphonates. This enablesformulation into systems where an anionic containing polymer providesbenefit and where non-detrimental effects of consumption and waterstability are a must.

In certain embodiments, the present invention is directed to oral carecompositions including a novel polymer comprising a phosphono-phosphategroup and an anionic group wherein said phosphono-phosphate group hasthe structure of Formula 1:

-   -   wherein:        -   ε is the site of attachment to a carbon atom in the polymer            backbone, side group, or side chain;        -   R₁ is selected from the group consisting of —H, alkyl,            alkanediyl-alkoxy, metal salt having Na, K, Ca, Mg, Mn, Zn,            Fe, or Sn cation, amine cation salt, and a structure of            Formula 2:

-   -   -   -   wherein:            -   θ is the site of attachment to Formula 1,            -   R₄ and R₅ are independently selected from the group                consisting of —H, alkyl, alkanediyl-alkoxy, metal salt                having Na, K, Ca, Mg, Mn, Zn, Fe, or Sn cation, and                amine cation salt;

        -   R₂ is selected from the group consisting of —H, alkyl,            alkanediyl-alkoxy, metal salt having Na, K, Ca, Mg, Mn, Zn,            Fe, or Sn cation, amine cation salt, and a structure of            Formula 3:

-   -   -   -   wherein:            -   θ is the site of attachment to Formula 1,            -   R₆, and R₇ are independently selected from the group                consisting of —H, alkyl, alkanediyl-alkoxy, metal salt                having Na, K, Ca, Mg, Mn, Zn, Fe, or Sn cation, and                amine cation salt, and            -   n is an integer from 1 to 22; and

        -   R₃ is selected from the group consisting of —H, alkyl,            alkanediyl-alkoxy, metal salt having Na, K, Ca, Mg, Mn, Zn,            Fe, or Sn cation, and amine cation salt;

        -   and said anionic group is covalently bound to the polymer            backbone, side group, or side chain and is selected from the            chemical group consisting of phosphate, phosphonate,            phosphinate, sulfate, sulfonate, sulfinate, mercapto,            carboxylate, hydroxyamino, amine oxide, and hydroxamate.

In certain embodiments, at least one monomer used to create the polymercomprises the phosphono-phosphate group. In another embodiment, at leastone monomer used to create the polymer comprises the anionic group. Inanother embodiment, at least one monomer used to create said polymercomprises said anionic group and at least one monomer used to createsaid polymer comprises said phosphono-phosphate group. In anotherembodiment, the phosphono-phosphate group is added during apost-polymerization modification.

In certain embodiments, when at least one monomer used to create thepolymer comprises the phosphono-phosphate group, said at least onemonomer has the structure of Formula 4:

-   -   wherein:        -   β is the site of attachment to the phosphono-phosphate group            of Formula 1;        -   R₈ is selected from the group consisting of —H and —CH₃;        -   L₁ is selected from the group consisting of a chemical bond,            arenediyl, and a structure of Formula 5:

-   -   wherein:        -   α is the site of attachment to the alkenyl radical in            Formula 4;        -   β is the site of attachment to the phosphono-phosphate group            of Formula 1;        -   X is selected from the group consisting of the structures in            Formulas 6-12;

-   -   wherein:        -   R₉ is selected from the group consisting of —H,            alkyl_((C1-8)), phosphonoalkyl, and            phosphono(phosphate)alkyl; and    -   Y is selected from the group consisting of alkanediyl,        alkoxydiyl, alkylaminodiyl and alkenediyl.

In certain embodiments, when at least one monomer used to create thepolymer comprises the phosphono-phosphate group, and said at least onemonomer has the structure of Formula 4, L₁ is a covalent bond. Inanother embodiment, when at least one monomer used to create the polymercomprises the phosphono-phosphate group, and said at least one monomerhas the structure of Formula 4, L₁ has the structure of Formula 5. Inanother embodiment, when at least one monomer used to create the polymercomprises the phosphono-phosphate group, said at least one monomer hasthe structure of Formula 4, and L₁ has the structure of Formula 5, thestructure of X is selected from the group consisting of Formula 6,Formula 9 and Formula 11.

In certain embodiments, said anionic group is selected from phosphate,phosphonate, sulfate, sulfonate or carboxylate. In another embodiment,said anionic group is sulfonate. In another embodiment, said anionicgroup is carboxylate. In another embodiment, said anionic group isphosphonate.

In certain embodiments, when at least one monomer used to create thepolymer comprises an anionic group, said at least one monomer furthercomprises an alkenyl group of the structure of Formula 13:

-   -   wherein:        -   R₁₀ is selected from the group consisting of H or CH₃ and L₂            is a linking group to the anionic group.

In certain embodiments, when at least one monomer used to create thepolymer comprises an anionic group, said at least one monomer furthercomprises an alkenyl group of the structure of Formula 14:

-   -   wherein:        -   R₁₁ is selected from the group consisting of H and alkyl;        -   δ is the site of attachment to the anionic group;        -   L₃ is selected from the group consisting of a chemical bond,            arenediyl, and a structure of Formula 15;

-   -   wherein:        -   γ is the site of attachment to the alkenyl radical;        -   δ is the site of attachment to the anionic group;        -   W is selected from the structures in Formulas 16-22:

-   -   wherein:        -   R₁₂ is selected from the group consisting of —H, and            alkyl_((C1-8)); and        -   V is selected from the group consisting of alkanediyl,            alkoxydiyl, alkylaminodiyl, and alkenediyl.

In certain embodiments, when at least one monomer used to create thepolymer comprises an anionic group, said at least one monomer isselected from the group consisting of vinyl phosphonate, vinylsulfonate, acrylate, methyl vinyl phosphonate, methyl vinyl sulfonate,methacrylate, styrene phosphonate, styrene sulfonate, vinyl benzenephosphonate, vinyl benzene sulfonate, 2-acrylamido-2-methyl propanesulfonate (AMPS), and 2-Sulfopropyl Acrylate (SPA).

In certain embodiments, when at least one monomer used to create saidpolymer comprises said anionic group and at least one monomer used tocreate said polymer comprises said phosphono-phosphate group, the ratioof said at least one monomer comprising said phosphono-phosphate groupto said at least one monomer comprising said anionic group ranges from99.9:0.1 to 0.1:99.9, respectively.

In certain embodiments, when at least one monomer used to create saidpolymer comprises said anionic group and at least one monomer used tocreate said polymer comprises said phosphono-phosphate group, the ratioof said at least one monomer comprising said phosphono-phosphate groupto said at least one monomer comprising said anionic group ranges from99:1 to 1:99, respectively.

In certain embodiments, when at least one monomer used to create saidpolymer comprises said anionic group and at least one monomer used tocreate said polymer comprises said phosphono-phosphate group, the ratioof said at least one monomer comprising said phosphono-phosphate groupto said at least one monomer comprising said anionic group ranges from90:10 to 10:90, respectively.

In certain embodiments, when at least one monomer used to create saidpolymer comprises said anionic group and at least one monomer used tocreate said polymer comprises said phosphono-phosphate group, the ratioof said at least one monomer comprising said phosphono-phosphate groupto said at least one monomer comprising said anionic group ranges from70:30 to 30:70, respectively.

The foregoing summary is not intended to define every aspect of theinvention, and additional aspects are described in other sections, suchas the Detailed Description. In addition, the invention includes, as anadditional aspect, all embodiments of the invention narrower in scope inany way than the variations defined by specific paragraphs set forthherein. For example, certain aspects of the invention that are describedas a genus, and it should be understood that every member of a genus is,individually, an aspect of the invention. Also, aspects described as agenus or selecting a member of a genus should be understood to embracecombinations of two or more members of the genus.

These and other features, aspects, and advantages of the presentinvention will become evident to those skilled in the art from readingof the present disclosure.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a chart showing polymer performance.

FIG. 2 is a chart showing polymer performance.

FIG. 3 is a chart showing polymer performance.

FIG. 4 is a chart showing polymer performance.

FIG. 5 is a GPC trace plot resulting from polymer analysis.

FIG. 6 is a GPC trace plot resulting from polymer analysis.

DETAILED DESCRIPTION OF THE INVENTION

While the specification concludes with claims particularly pointing anddistinctly claiming the invention, it is believed the present inventionwill be better understood from the following description.

All percentages herein are by moles of the compositions unless otherwiseindicated.

All ratios are molar ratios unless otherwise indicated.

All percentages, ratios, and levels of ingredients referred to hereinare based on the actual amount of the ingredient by moles, and do notinclude solvents, fillers, or other materials with which the ingredientmay be combined as commercially available products, unless otherwiseindicated.

As used herein, “comprising” means that other steps and otheringredients which do not affect the end result can be added. This termencompasses the terms “consisting of” and “consisting essentially of”.

All cited references are incorporated herein by reference in theirentireties. Citation of any reference is not an admission regarding anydetermination as to its availability as prior art to the claimedinvention.

Definitions

The terms “site” or “site of attachment” or “point of attachment” allmean an atom having an open valence within a chemical group or definedstructural entity that is designated with a symbol such as a simple dash(-) or a lower case letter from the greek alphabet followed by a dash ora line (e.g. α-, β-, etc.) to indicate that the so-designated atomconnects to another atom in a separate chemical group via a chemicalbond. The symbol “

” when drawn perpendicular across a bond

also indicates a point of attachment of a chemical group. It is notedthat the point of attachment is typically only identified in this mannerfor larger chemical groups in order to unambiguously assist the readerin identifying the point of attachment to the atom from which the bondextends. A site or point of attachment on a first chemical group ordefined structural entity connects to a site or point of attachment on asecond chemical group or defined structural entity via either single,double, or triple covalent bonds in order to satisfy the normal valencyof the atoms connected.

The term “radical” when used with a chemical group indicates anyconnected group of atoms, such as a methyl group, a carboxyl group, or aphosphono-phosphate group that is part of a larger molecule.

When used in the context of a chemical group: “hydrogen” means —H;“hydroxy” means —OH; “oxo” means ═O; “carbonyl” means —C(═O)—; “carboxy”and “carboxylate” mean —C(═O)OH (also written as —COOH or —CO2H) or adeprotonated form thereof; “amino” means —NH2; “hydroxyamino” means—NHOH; “nitro” means —NO2; “imino” means ═NH; “amine oxide” means N⁺O⁻where N has three covalent bonds to atoms other than O; “hydroxamic” or“hydroxamate” means —C(O)NHOH or a deprotonated form thereof; in amonovalent context “phosphate” means —OP(O)(OH)₂ or a deprotonated formthereof; in a divalent context “phosphate” means —OP(O)(OH)O— or adeprotonated form thereof; “phosphonate” means C—P(O)(OH)₂ or adeprotonated form thereof, where the C has a normal valence of four andthree covalent bonds to atoms other than P; “phosphono-phosphate” meansa phosphonate that is chemically bound through a shared oxygen atom toat least one phosphate such as but not limited tophosphono-monophosphate C—P(O)(OH)OP(O)(OH)₂, phosphono-diphosphateC—P(O)(OP(O)(OH)₂)OP(O)(OH)₂, phosphono-cyclodiphosphate

phosphono-pyrophosphate C—P(O)(OH)OP(O)(OH)OP(O)(OH)₂, andphosphono-polyphosphate C—P(O)(OH)(OP(O)(OH))_(n)OP(O)(OH)₂, where n isan integer between 1 and 100, or a deprotonated form thereof, where theC has a normal valence of four and three covalent bonds to atoms otherthan P; “phosphinate” means C—P(O)(OH)(C) or a deprotonated formthereof, where both C have a normal valence of four and three additionalbonds to atoms other than P; “sulfate” means —OS(O)₂OH or deprotonatedform thereof; “sulfonate” means CS(O)₂OH or a deprotonated form thereofwhere the C has a normal valence of four and three additional bonds toatoms other than S; “sulfinate” means CS(O)OH or a deprotonated formthereof, where the C has a normal valence of four and three additionalbonds to atoms other than S; “mercapto” means —SH; “thio” means =S;“sulfonyl” means —S(O)2-; and “sulfinyl” means —S(O)—.

For the chemical groups and classes below, the following parentheticalsubscripts further define the chemical group/class as follows: “(Cn)”defines the exact number (n) of carbon atoms in the chemicalgroup/class. “(C≤n)” defines the maximum number (n) of carbon atoms thatcan be in the chemical group/class, with the minimum number as small aspossible for the chemical group in question, e.g., it is understood thatthe minimum number of carbon atoms in the chemical group“alkenyl_((C≤8))” or the chemical class “alkene_((C≤8))” is two. Forexample, “alkoxy_((C≤8))” designates those alkoxy groups having from 1to 8 carbon atoms. (C_(n-n)′) defines both the minimum (n) and maximumnumber (n′) of carbon atoms in the chemical group. Similarly,alkyl_((C2-8)) designates those alkyl groups having from 2 to 8 carbonatoms, inclusive.

The term “cation” refers to an atom, molecule, or a chemical group witha net positive charge including single and multiply charged species.Cations can be individual atoms such as metals, non-limiting examplesinclude Na⁺ or Ca⁺², individual molecules, non-limiting examples include(CH₃)₄N⁺, or a chemical group, non limiting examples include-N(CH₃)₃ ⁺.The term “amine cation” refers to a particular molecular cation, of theform NR₄ ⁺ where the four substituting R moieties can be independentlyselected from H and alkyl, non-limiting examples include NH₄ ⁺(ammonium), CH₃NH₃ ⁺ (methylammonium), CH₃CH₂NH₃ ⁺ (ethylammonium),(CH₃)₂NH₂ ⁺ (dimethylammonium), (CH₃)₃NH⁺ (trimethyl ammonium), and(CH₃)₄N⁺ (tetramethylammonium).

The term “anion” refers to an atom, molecule, or chemical group with anet negative charge including single and multiply charged species.Anions can be individual atoms, for example but not limited to halidesF⁻, Cl⁻, Br⁻, individual molecules, non limiting examples include CO₃⁻², H₂PO₄ ⁻, HPO₄ ⁻², PO₄ ⁻³, HSO₄ ⁻, SO₄ ⁻², or a chemical group, nonlimiting examples include sulfate, phosphate, sulfonate, phosphonate,phosphinate, sulfonate, mercapto, carboxylate, amine oxide, hydroxamateand hydroxyl amino. Deprotonated forms of previously defined chemicalgroups are considered anionic groups if the removal of the protonresults in a net negative charge. In solutions, chemical groups arecapable of losing a proton and become anionic as a function of pHaccording to the Henderson-Hasselbach equation (pH=pKa+log₁₀([A⁻]/[HA];where [HA] is the molar concentration of an undissociated acid and [A⁻]is the molar concentration of this acid's conjugate base). When the pHof the solution equals the pKa value of functional group, 50% of thefunctional group will be anionic, while the remaining 50% will have aproton. Typically, a functional group in solution can be consideredanionic if the pH is at or above the pKa of the functional group.

The term “salt” or “salts” refers to the charge neutral combination ofone or more anions and cations. For example, when R is denoted as a saltfor the carboxylate group, —COOR, it is understood that the carboxylate(—COO—) is an anion with a negative charge −1, and that the R is acation with a positive charge of +1 to form a charge neutral entity withone anion of charge −1, or R is a cation with a positive charge of +2 toform a charge neutral entity with two anions both of −1 charge.

The term “saturated” as used herein means the chemical compound or groupso modified has no carbon-carbon double and no carbon-carbon triplebonds, except as noted below. In the case of substituted versions ofsaturated chemical groups, one or more carbon oxygen double bond or acarbon nitrogen double bond may be present. When such a bond is present,then carbon-carbon double bonds that may occur as part of keto-enoltautomerism or imine/enamine tautomerism are not precluded.

The term “aliphatic” when used without the “substituted” modifiersignifies that the chemical compound/group so modified is an acyclic orcyclic, but non-aromatic hydrocarbon chemical compound or group. Inaliphatic chemical compounds/groups, the carbon atoms can be joinedtogether in straight chains, branched chains, or non-aromatic rings(alicyclic). Aliphatic chemical compounds/groups can be saturated, thatis joined by single bonds (alkanes/alkyl), or unsaturated, with one ormore double bonds (alkenes/alkenyl), or with one or more triple bonds(alkynes/alkynyl).

The term “alkyl” when used without the “substituted” modifier refers toa monovalent saturated aliphatic group with a carbon atom as the pointof attachment, a linear or branched, cyclo, cyclic, or acyclicstructure, and no atoms other than carbon and hydrogen. Thus, as usedherein cycloalkyl is a subset of alkyl, with the carbon atom that formsthe point of attachment also being a member of one or more non-aromaticring structures wherein the cycloalkyl group consists of no atoms otherthan carbon and hydrogen. As used herein, the term does not preclude thepresence of one or more alkyl groups (carbon number limitationpermitting) attached to the ring or ring system. The groups —CH₃ (Me),—CH₂CH₃ (Et), —CH₂CH₂CH₃ (n-Pr or propyl), —CH(CH₃)₂ (i-Pr, ′Pr, orisopropyl), —CH(CH₂)₂ (cyclopropyl), —CH₂CH₂CH₂CH₃ (n-Bu),—CH(CH₃)CH₂CH₃ (sec-butyl), —CH₂CH(CH₃)₂ (isobutyl), —C(CH₃)₃(tertbutyl, t-butyl, t-Bu, or tBu), —CH₂C(CH₃)₃ (neo-pentyl),cyclobutyl, cyclopentyl, cyclohexyl, and cyclohexylmethyl arenon-limiting examples of alkyl groups. The term “alkanediyl” when usedwithout the “substituted” modifier refers to a divalent saturatedaliphatic group, with one or two saturated carbon atom(s) as thepoint(s) of attachment, a linear or branched, cyclo, cyclic or acyclicstructure, no carbon-carbon double or triple bonds, and no atoms otherthan carbon and hydrogen. The groups, —CH₂— (methylene), —CH₂CH₂—,—CH₂C(CH₃)₂CH₂—, and —CH₂CH₂CH₂— are non-limiting examples of alkanediylgroups. The term “alkylidene” when used without the “substituted”modifier refers to the divalent group ═CRR′ in which R and R′ areindependently hydrogen, alkyl, or R and R′ are taken together torepresent an alkanediyl having at least two carbon atoms. Non-limitingexamples of alkylidene groups include: ═CH₂, ═CH(CH₂CH₃), and ═C(CH₃)₂.An “alkane” refers to the compound H—R, wherein R is alkyl as this termis defined above. When any of these terms is used with the “substituted”modifier one or more hydrogen atom has been independently replaced by—OH, —F, —Cl, —Br, —I, —NH₂, —NO₂, —CO₂H, —CO₂CH₃, —CN, —SH, —OCH₃,—OCH₂CH₃, —C(O)CH₃, —NHCH₃, —NHCH₂CH₃, —N(CH₃)₂, —C(O)NH₂, —OC(O)CH₃,—S(O)₂NH₂, —P(O)(OH)₂, —P(O)(OH)OP(O)(OH)₂, —OP(O)(OH)₂,—OP(O)(OH)OP(O)(OH)₂, —S(O)₂(OH), or —OS(O)₂(OH). The following groupsare non-limiting examples of substituted alkyl groups: —CH₂OH, —CH₂Cl,—CF₃, —CH₂CN, —CH₂C(O)OH, —CH₂C(O)OCH₃, —CH₂C(O)NH₂, —CH₂C(O)CH₃,—CH₂OCH₃, —CH₂OC(O)CH₃, —CH₂NH₂, —CH₂N(CH₃)₂, —CH₂CH₂Cl, —CH₂P(O)(OH)₂,—CH₂P(O)(OH)OP(O)(OH)₂, —CH₂S(O)₂(OH), and —CH₂OS(O)₂(OH). The term“haloalkyl” is a subset of substituted alkyl, in which one or morehydrogen atoms has been substituted with a halo group and no other atomsaside from carbon, hydrogen and halogen are present. The group, —CH₂Clis a non-limiting example of a haloalkyl. The term “fluoroalkyl” is asubset of substituted alkyl, in which one or more hydrogen has beensubstituted with a fluoro group and no other atoms aside from carbon,hydrogen and fluorine are present. The groups, —CH₂F, —CF₃, and —CH₂CF₃are non-limiting examples of fluoroalkyl groups.

The term “phosphonoalkyl” is a subset of substituted alkyl, in which oneor more of the hydrogen has been substituted with a phosphonate groupand no other atoms aside from carbon, hydrogen, phosphorous, and oxygenare present. The groups, —CH₂P(O)(OH)₂, and —CH₂CH₂P(O)(OH)₂, and thecorresponding deprotonated forms thereof, are non-limiting examples of aphosphonoalkyl.

The term “phosphono(phosphate)alkyl” is a subset of substituted alkyl,in which one or more of the hydrogen has been substituted with aphosphono-phosphate group and no other atoms aside from carbon,hydrogen, phosphorous, and oxygen are present. The groups,—CH₂P(O)(OH)OP(O)(OH)₂, and —CH₂CH₂P(O)(OH)OP(O)(OH)₂, and correspondingdeprotonated forms thereof, are non-limiting examples ofphosphono(phosphate)alkyl.

The term “sulfonoalkyl” is a subset of substituted alkyl, in which oneor more of the hydrogen has been substituted with a sulfonate group andno other atoms aside from carbon, hydrogen, sulfur, and oxygen arepresent. The groups, —CH₂S(O)₂OH and —CH₂CH₂S(O)₂OH, and thecorresponding deprotonated forms thereof, are non-limiting examples of asulfonoalkyl.

The term “alkenyl” when used without the “substituted” modifier refersto an monovalent unsaturated aliphatic group with a carbon atom as thepoint of attachment, a linear or branched, cyclo, cyclic or acyclicstructure, at least one nonaromatic carbon-carbon double bond, nocarbon-carbon triple bonds, and no atoms other than carbon and hydrogen.Non-limiting examples of alkenyl groups include: —CH═CH₂ (vinyl),—C(CH₃)═CH₂ (methyl-vinyl), —CH═CHCH₃, —CH═CHCH₂CH₃, —CH₂CH═CH₂ (allyl),—CH₂CH═CHCH₃, and —CH═CHCH═CH₂. The term “alkenediyl” when used withoutthe “substituted” modifier refers to a divalent unsaturated aliphaticgroup, with two carbon atoms as points of attachment, a linear orbranched, cyclo, cyclic or acyclic structure, at least one nonaromaticcarbon-carbon double bond, no carbon-carbon triple bonds, and no atomsother than carbon and hydrogen. The groups, >C═CH₂ (vinylidine),—CH═CH—, —CH═C(CH₃)CH₂—, and —CH═CHCH₂—, are non-limiting examples ofalkenediyl groups. It is noted that while the alkenediyl group isaliphatic, once connected at both ends, this group is not precluded fromforming part of an aromatic structure. The terms “alkene” or “olefin”are synonymous and refer to a compound having the formula H—R, wherein Ris alkenyl as this term is defined above. A “terminal alkene” refers toan alkene having just one carbon-carbon double bond, wherein that bondforms a vinyl group at one end of the molecule. When any of these termsare used with the “substituted” modifier one or more hydrogen atom hasbeen independently replaced by —OH, —F, —Cl, —Br, —I, —NH, —NO₂, —CO₂H,—CO₂CH₃, —CN, —SH, —OCH₃, —OCH₂CH₃, —C(O)CH₃, —NHCH₃, —NHCH₂CH₃,—N(CH₃)₂, —C(O)NH₂, —OC(O)CH₃, or —S(O)₂NH₂. The groups, —CH═CHF,—CH═CHCl and —CH═CHBr, are non-limiting examples of substituted alkenylgroups.

The term “alkynyl” when used without the “substituted” modifier refersto an monovalent unsaturated aliphatic group with a carbon atom as thepoint of attachment, a linear or branched, cyclo, cyclic or acyclicstructure, at least one carbon-carbon triple bond, and no atoms otherthan carbon and hydrogen. As used herein, the term alkynyl does notpreclude the presence of one or more non-aromatic carbon-carbon doublebonds. The groups, —C≡CH, —C≡CCH₃, and —CH₂C≡CCH₃, are non-limitingexamples of alkynyl groups. An “alkyne” refers to the compound H—R,wherein R is alkynyl. When any of these terms are used with the“substituted” modifier one or more hydrogen atom has been independentlyreplaced by —OH, —F, —Cl, —Br, —I, —NH₂, —NO₂, —CO₂H, —CO₂CH₃, —CN, —SH,—OCH₃, —OCH₂CH₃, —C(O)CH₃, —NHCH₃, —NHCH₂CH₃, —N(CH₃)₂, —C(O)NH₂,—OC(O)CH₃, or —S(O)₂NH₂. The term “aryl” when used without the“substituted” modifier refers to a monovalent unsaturated aromatic groupwith an aromatic carbon atom as the point of attachment, said carbonatom forming part of a one or more six membered aromatic ring structure,wherein the ring atoms are all carbon, and wherein the group consists ofno atoms other than carbon and hydrogen. If more than one ring ispresent, the rings may be fused or unfused. As used herein, the termdoes not preclude the presence of one or more alkyl or aralkyl groups(carbon number limitation permitting) attached to the first aromaticring or any additional aromatic ring present. Non-limiting examples ofaryl groups include phenyl (-Ph), methylphenyl, (dimethyl)phenyl,—C₆H₄CH₂CH₃ (ethylphenyl), naphthyl, and a monovalent group derived frombiphenyl. The term “arenediyl” when used without the “substituted”modifier refers to a divalent aromatic group with two aromatic carbonatoms as points of attachment, said carbon atoms forming part of one ormore six-membered aromatic ring structure(s) wherein the ring atoms areall carbon, and wherein the monovalent group consists of no atoms otherthan carbon and hydrogen. As used herein, the term does not preclude thepresence of one or more alkyl, aryl or aralkyl groups (carbon numberlimitation permitting) attached to the first aromatic ring or anyadditional aromatic ring present. If more than one ring is present, therings may be fused or unfused. Unfused rings may be connected via one ormore of the following: a covalent bond, alkanediyl, or alkenediyl groups(carbon number limitation permitting). Non-limiting examples ofarenediyl groups include:

An “arene” refers to the compound H—R, wherein R is aryl as that term isdefined above. Benzene and toluene are non-limiting examples of arenes.When any of these terms are used with the “substituted” modifier one ormore hydrogen atom has been independently replaced by —OH, —F, —Cl, —Br,—I, —NH₂, —NO₂, —CO₂H, —CO₂CH₃, —CN, —SH, —OCH₃, —OCH₂CH₃, —C(O)CH₃,—NHCH₃, —NHCH₂CH₃, —N(CH₃)₂, —C(O)NH₂, —OC(O)CH₃, or —S(O)₂NH₂.

The term “acyl” when used without the “substituted” modifier refers tothe group —C(O)R, in which R is a hydrogen, alkyl, aryl, aralkyl orheteroaryl, as those terms are defined above. The groups, —CHO (formyl),—C(O)CH₃ (acetyl, Ac), —C(O)CH₂CH₃, —C(O)CH₂CH₂CH₃, —C(O)CH(CH₃)₂,—C(O)CH(CH₂)₂, —C(O)C₆H₅, —C(O)C₆H₄CH₃, —C(O)CH₂C₆H₅, —C(O)(imidazolyl)are non-limiting examples of acyl groups. A “thioacyl” is defined in ananalogous manner, except that the oxygen atom of the group —C(O)R hasbeen replaced with a sulfur atom, —C(S)R. The term “aldehyde”corresponds to an alkane, as defined above, wherein at least one of thehydrogen atoms has been replaced with a —CHO group. When any of theseterms are used with the “substituted” modifier one or more hydrogen atom(including a hydrogen atom directly attached the carbonyl orthiocarbonyl group, if any) has been independently replaced by —OH, —F,—Cl, —Br, —I, —NH2, —NO₂, —CO₂H, —CO₂CH₃, —CN, —SH, —OCH₃, —OCH₂CH₃,—C(O)CH₃, —NHCH₃, —NHCH₂CH₃, —N(CH₃)₂, —C(O)NH₂, —OC(O)CH₃, or—S(O)₂NH₂. The groups, —C(O)CH₂CF₃, —CO₂H (Carboxyl),—CO₂CH₃(methylcarboxyl), —CO₂CH₂CH₃, —C(O)NH₂ (Carbamoyl), and—CON(CH₃)₂, are non-limiting examples of substituted acyl groups.

The term “alkoxy” when used without the “substituted” modifier refers tothe group —OR, in which R is an alkyl, as that term is defined above.Non-limiting examples of alkoxy groups include: —OCH₃ (methoxy),—OCH₂CH₃ (ethoxy), —OCH₂CH₂CH₃, —OCH(CH₃)₂ (isopropoxy), —O(CH₃)₃(tert-butoxy), —OCH(CH₂)₂, —O-cyclopentyl, and —O-cyclohexyl. The terms“alkenyloxy”, “alkynyloxy”, “aryloxy”, “aralkoxy”, “heteroaryloxy”,“heterocycloalkoxy”, and “acyloxy”, when used without the “substituted”modifier, refers to groups, defined as —OR, in which R is alkenyl,alkynyl, aryl, aralkyl, heteroaryl, heterocycloalkyl, and acyl,respectively. The term “alkoxydiyl” refers to the divalent group—O-alkanediyl-, —O-alkanediyl-O—, or -alkanediyl-O-alkanediyl-. The term“alkanediyl-alkoxy” refers to -alkanediyl-O-alkyl. A nonlimiting exampleof alkanedyl-alkoxy is CH₂—CH₂—O—CH₂—CH₃. The term “alkylthio” and“acylthio” when used without the “substituted” modifier refers to thegroup —SR, in which R is an alkyl and acyl, respectively. The term“alcohol” corresponds to an alkane, as defined above, wherein at leastone of the hydrogen atoms has been replaced with a hydroxy group. Theterm “ether” corresponds to an alkane, as defined above, wherein atleast one of the hydrogen atoms has been replaced with an alkoxy group.When any of these terms is used with the “substituted” modifier one ormore hydrogen atom has been independently replaced by —OH, —F, —Cl, —Br,—I, —NH₂, —NO₂, —CO₂H, —CO₂CH₃, —CN, —SH, —OCH₃, —OCH₂CH₃, —C(O)CH₃,—NHCH₃, —NHCH₂CH₃, —N(CH₃)₂, —C(O)NH₂, —OC(O)CH₃, or —S(O)₂NH₂.

The term “alkylamino” when used without the “substituted” modifierrefers to the group —NHR, in which R is an alkyl, as that term isdefined above. Non-limiting examples of alkylamino groups include:—NHCH₃ and —NHCH₂CH₃. The term “dialkylamino” when used without the“substituted” modifier refers to the group —NRR′, in which R and R′ canbe the same or different alkyl groups, or R and R′ can be taken togetherto represent an alkanediyl. Non-limiting examples of dialkylamino groupsinclude: —N(CH₃)₂, —N(CH₃)(CH₂CH₃), and N-pyrrolidinyl. The terms“alkoxyamino”, “alkenylamino”, “alkynylamino”, “arylamino”,“aralkylamino”, “heteroarylamino”, “heterocycloalkylamino” and“alkylsulfonylamino” when used without the “substituted” modifier,refers to groups, defined as —NHR, in which R is alkoxy, alkenyl,alkynyl, aryl, aralkyl, heteroaryl, heterocycloalkyl, and alkylsulfonyl,respectively. A non-limiting example of an arylamino group is —NHC₆H₅.The term “amido” (acylamino), when used without the “substituted”modifier, refers to the group —NHR, in which R is acyl, as that term isdefined above. A non-limiting example of an amido group is —NHC(O)CH₃.The term “alkylimino” when used without the “substituted” modifierrefers to the divalent group ═NR, in which R is an alkyl, as that termis defined above. The term “alkylaminodiyl” refers to the divalent group—NH-alkanediyl-, —NH-alkanediyl-NH—, or -alkanediyl-NH-alkanediyl-. Whenany of these terms is used with the “substituted” modifier one or morehydrogen atom has been independently replaced by —OH, —F, —Cl, —Br, —I,—NH₂, —NO₂, —CO₂H, —CO₂CH₃, —CN, —SH, —OCH₃, —OCH₂CH₃, —C(O)CH₃, —NHCH₃,—NHCH₂CH₃, —N(CH₃)₂, —C(O)NH₂, —OC(O)CH₃, or —S(O)₂NH₂. The groups—NHC(O)OCH₃ and —NHC(O)NHCH₃ are non-limiting examples of substitutedamido groups.

The terms “alkylsulfonyl” and “alkylsulfinyl” when used without the“substituted” modifier refers to the groups —S(O)₂R and —S(O)R,respectively, in which R is an alkyl, as that term is defined above. Theterms “alkenylsulfonyl”, “alkynylsulfonyl”, “arylsulfonyl”,“aralkylsulfonyl”, “heteroarylsulfonyl”, and “heterocycloalkylsulfonyl”are defined in an analogous manner. When any of these terms is used withthe “substituted” modifier one or more hydrogen atom has beenindependently replaced by —OH, —F, —Cl, —Br, —I, —NH2, —NO₂, —CO₂H,—CO₂CH₃, —CN, —SH, —OCH₃, —OCH₂CH₃, —C(O)CH₃, —NHCH₃, —NHCH₂CH₃,—N(CH₃)₂, —C(O)NH₂, —OC(O)CH₃, or —S(O)₂NH₂.

The term “alkylphosphate” when used without the “substituted” modifierrefers to the group —OP(O)(OH)(OR) or a deprotonated form thereof, inwhich R is an alkyl, as that term is defined above. Nonlimiting examplesof alkylphosphate groups include: —OP(O)(OH)(OMe) and —OP(O)(OH)(OEt).The term “dialkylphosphate” when used without the “substituted” modifierrefers to the group —OP(O)(OR)(OR′), in which R and R′ can be the sameor different alkyl groups, or R and R′ can be taken together torepresent an alkanediyl. Non-limiting examples of dialkylphosphategroups include: —OP(O)(OMe)₂, —OP(O)(OEt)(OMe) and —OP(O)(OEt)₂. Whenany of these terms is used with the “substituted” modifier one or morehydrogen atom has been independently replaced by —OH, —F, —Cl, —Br, —I,—NH₂, —NO₂, —CO₂H, —CO₂CH₃, —CN, —SH, —OCH₃, —OCH₂CH₃, —C(O)CH₃, —NHCH₃,—NHCH₂CH₃, —N(CH₃)₂, —C(O)NH₂, —OC(O)CH₃, or —S(O)₂NH₂.

Linking group means either a covalent bond between two other definedgroups, or a series of covalently bound atoms that connect two otherdefined groups where in the series of covalently bound atoms have noopen valences other than the sites of attachment to the two otherdefined groups. Non-limiting examples of a linking group include acovalent bond, alkanediyl, alkenediyl, arenediyl, alkoxydiyl, andalkylaminodiyl.

As used herein, a “chiral auxiliary” refers to a removable chiral groupthat is capable of influencing the stereoselectivity of a reaction.Persons of skill in the art are familiar with such compounds, and manyare commercially available.

Other abbreviations used herein are as follows: DMSO, dimethylsulfoxide; DMF, dimethylformamide; MeCN, acetonitrile; MeOH, methanol;EtOH, ethanol; EtOAc, ethyl acetate; tBuOH, tert-butanol; iPrOH,isopropanol; cHexOH, cyclohexanol; Ac₂O, acetic anhydride; AcOOH,peracetic acid; HCO₂Et, ethyl formate; THF, tetrahydrofuran; MTBE,methyl tert-butyl ether; DME, dimethoxyethane; NBS, N-bromosuccinimide;CDI, carbonyldiimidazole; DIEA, diisopropylethylamine; TEA,triethylamine; DMAP, dimethylaminopyridine; NaOH, sodium hydroxide;AAPH, 2,2′-azobis(2-methylpropionamidine) dihydrochloride; CTA,1-Octanethiol; APS, ammonium persulfate; TMP, trimethyl phosphate; VPA,vinyl phosphonic acid; VPP, vinyl phosphono-monophosphate; VPPP, vinylphosphono-pyrophosphate MVPP, methyl-vinyl phosphono-monophosphate; SVS,sodium vinyl sulfonate; AMPS, sodium 2-acrylamido-2-methyl propanesulfonic acid; SPA, 3-sulfopropyl acrylate potassium salt; 22A2MPA2HCl,2,2′-azobis (2-methylpropionamidine) dihydrochloride; VBPP,(4-vinylbenzyl)monophosphono-phosphate; VSME, vinyl sulfonate methylester; NaOMe, sodium methoxide; NaCl, sodium chloride; DMVP, dimethylvinyl phosphonate

A “monomer molecule” is defined by the International Union of Pure andApplied Chemistry (IUPAC) as “A molecule which can undergopolymerization thereby contributing constitutional units to theessential structure of a macromolecule.” A polymer is a macromolecule.

A “polymer backbone” or “main chain” is defined by IUPAC as “That linearchain to which all other chains, long or short, or both may be regardedas being pendant” with the note that “Where two or more chains couldequally be considered to be the main chain, that one is selected whichleads the simplest representation of the molecule.” Backbones can be ofdifferent chemical compositions depending upon the starting materialsfrom which they are made. Common backbones from chemically andbiologically synthesized polymers include alkanes, typically from vinylor methyl vinyl polymerizations or cationic and anionic polymerizations,poly esters, from condensation polymerizations, poly amides, such aspoly peptides from polymerizations involving amidation reactions, andpoly ethoxylates from epoxide ring opening.

A “pendant group” or “side group” is defined by IUPAC as “An offshoot,neither oligomeric nor polymeric from a chain.” A side group as suchdoes not include a linear repeated unit.

A “polymer side chain” or “pendant chain” is defined by IUPAC as “Anoligomeric or polymeric offshoot from a macromolecular chain” with theadditional notes that “An oligomeric branch may be termed a short chainbranch” and “A polymeric branch may be termed a long chain branch”.

“Post-polymerization modification” is defined as any reaction ortreatment of a polymer that takes place following polymerization.Post-polymerization modifications include reactions to chemical groupswithin or attached to the polymer backbone, pendant group, or polymerside chains.

By “personal care composition” is meant a product, which in the ordinarycourse of usage is applied to or contacted with a body surface toprovide a beneficial effect. Body surface includes skin, for exampledermal or mucosal; body surface also includes structures associated withthe body surface for example hair, teeth, or nails. Examples of personalcare compositions include a product applied to a human body forimproving appearance, cleansing, and odor control or general aesthetics.Non-limiting examples of personal care compositions include oral carecompositions, such as, dentifrice, mouth rinse, mousse, foam, mouthspray, lozenge, chewable tablet, chewing gum, tooth whitening strips,floss and floss coatings, breath freshening dissolvable strips, denturecare product, denture adhesive product; after shave gels and creams,pre-shave preparations, shaving gels, creams, or foams, moisturizers andlotions; cough and cold compositions, gels, gel caps, and throat sprays;leave-on skin lotions and creams, shampoos, body washes, body rubs, suchas Vicks Vaporub; hair conditioners, hair dyeing and bleachingcompositions, mousses, shower gels, bar soaps, antiperspirants,deodorants, depilatories, lipsticks, foundations, mascara, sunlesstanners and sunscreen lotions; feminine care compositions, such aslotions and lotion compositions directed towards absorbent articles;baby care compositions directed towards absorbent or disposablearticles; and oral cleaning compositions for animals, such as dogs andcats.

The term “dentifrice”, as used herein, includes tooth orsubgingival-paste, gel, or liquid formulations unless otherwisespecified. The dentifrice composition may be a single phase compositionor may be a combination of two or more separate dentifrice compositions.The dentifrice composition may be in any desired form, such as deepstriped, surface striped, multilayered, having a gel surrounding apaste, or any combination thereof. Each dentifrice composition in adentifrice comprising two or more separate dentifrice compositions maybe contained in a physically separated compartment of a dispenser anddispensed side-by-side.

The term “dispenser”, as used herein, means any pump, tube, or containersuitable for dispensing compositions such as dentifrices.

The term “teeth”, as used herein, refers to natural teeth as well asartificial teeth or dental prosthesis.

The term “orally acceptable carrier or excipients” includes safe andeffective materials and conventional additives used in oral carecompositions including but not limited to fluoride ion sources,anti-calculus or anti-tartar agents, buffers, abrasives such as silica,alkali metal bicarbonate salts, thickening materials, humectants, water,surfactants, titanium dioxide, flavorants, sweetening agents, xylitol,coloring agents, and mixtures thereof.

Herein, the terms “tartar” and “calculus” are used interchangeably andrefer to mineralized dental plaque biofilms.

As used herein, the word “or” when used as a connector of two or moreelements is meant to include the elements individually and incombination; for example X or Y, means X or Y or both.

The use of the word “a” or “an,” when used in conjunction with the term“comprising” in the claims and/or the specification may mean “one,” butit is also consistent with the meaning of “one or more,” “at least one,”and “one or more than one.”

Throughout this application, the term “about” is used to indicate that avalue includes the inherent variation of error for the device, themethod being employed to determine the value, or the variation thatexists among the study subjects.

The terms “comprise,” “have” and “include” are open ended linking verbs.Any forms or tenses of one or more of these verbs, such as “comprises,”“comprising,” “has,” “having,” “includes” and “including,” are alsoopen-ended. For example, any method that “comprises,” “has” or“includes” one or more steps is not limited to possessing only those oneor more steps and also covers other unlisted steps.

The above definitions supersede any conflicting definition in anyreference that is incorporated by reference herein. The fact thatcertain terms are defined, however, should not be considered asindicative that any term that is undefined is indefinite. Rather, allterms used are believed to describe the invention in terms such that oneof ordinary skill can appreciate the scope and practice the presentinvention.

Phosphono-Phosphate and Anionic Containing Polymers

The present invention is directed to a novel polymer comprising aphosphono-phosphate group and an anionic group. It is recognized thatthe phosphono-phosphate group can be anionic in nature depending uponthe substituents upon it and the environment into which it is placed.For the purpose of clarity, anionic group in this application refers toan anionic group other than phosphono-phosphate.

In certain embodiments, the present invention is directed to a novelpolymer comprising a phosphono-phosphate group and an anionic groupwherein said phosphono-phosphate group has the structure of Formula 1:

-   -   wherein:        -   ε is the site of attachment to a carbon atom in the polymer            backbone, side group, or side chain;        -   R₁ is selected from the group consisting of —H, alkyl,            alkanediyl-alkoxy, metal salt having Na, K, Ca, Mg, Mn, Zn,            Fe, or Sn cation, amine cation salt, and a structure of            Formula 2:

-   -   -   -   wherein:            -   θ is the site of attachment to Formula 1,            -   R₄ and R₅ are independently selected from the group                consisting of —H, alkyl, alkanediyl-alkoxy, metal salt                having Na, K, Ca, Mg, Mn, Zn, Fe, or Sn cation, and                amine cation salt;

        -   R₂ is selected from the group consisting of —H, alkyl,            alkanediyl-alkoxy, metal salt having Na, K, Ca, Mg, Mn, Zn,            Fe, or Sn cation, amine cation salt, and a structure of            Formula 3:

-   -   -   -   wherein:            -   θ is the site of attachment to Formula 1,            -   R₆, and R₇ are independently selected from the group                consisting of —H, alkyl, alkanediyl-alkoxy, metal salt                having Na, K, Ca, Mg, Mn, Zn, Fe, or Sn cation, and                amine cation salt, and            -   n is an integer from 1 to 22; and

        -   R₃ is selected from the group consisting of —H, alkyl,            alkanediyl-alkoxy, metal salt having Na, K, Ca, Mg, Mn, Zn,            Fe, or Sn cation, and amine cation salt,

        -   and said anionic group is covalently bound to the polymer            backbone, side group, or side chain and is selected from the            chemical group consisting of phosphate, phosphonate,            phosphinate, sulfate, sulfonate, sulfinate, mercapto,            carboxylate, hydroxyamino, amine oxide, and hydroxamate.

In certain embodiments, at least one monomer used to create the polymercomprises the phosphono-phosphate group. In another embodiment, at leastone monomer used to create the polymer comprises the anionic group. Inanother embodiment, at least one monomer used to create said polymercomprises said anionic group and at least one monomer used to createsaid polymer comprises said phosphono-phosphate group. In anotherembodiment, the phosphono-phosphate group is added during apost-polymerization modification.

In certain embodiments of the polymer, R₁, R₂, and R₃ are independentlyselected from the group consisting of H, Na salt, and K salt. In certainembodiments of the polymer, R₁, R₂, and R₃ are independently selectedfrom the group consisting of H, Na salt, K salt, Zn salt, Ca salt, Snsalt, and amine cation salt.

In another embodiment of the polymer, R₁ has the structure of Formula 2.In a further embodiment of the polymer, R₁ has the structure of Formula2 and R₄ and R₅ are independently selected from H, Na salt, and K salt.In a further embodiment of the polymer, R₁ has the structure of Formula2 and R₄ and R₅ are independently selected from H, Na salt, K salt, Znsalt, Ca salt, Sn salt, and amine cation salt.

In another embodiment of the polymer, R₂ has the structure of Formula 3.In another embodiment of the polymer R₂ has the structure of Formula 3and n is an integer from 1 to 3. In another embodiment of the polymer,R₂ has the structure of Formula 3 and n is 1. In another embodiment ofthe polymer, R₂ has the structure of Formula 3 and R₆ and R₇ areindependently selected from the group consisting of H, Na salt, and Ksalt. In another embodiment of the polymer, R₂ has the structure ofFormula 3 and R₆ and R₇ are independently selected from the groupconsisting of H, Na salt, K salt, Zn salt, Ca salt, Sn salt, and aminecation salt. In another embodiment of the compound, R₂ has the structureof Formula 3, R₆ and R₇ are independently selected from the groupconsisting of H, Na salt, K salt, Zn salt, Ca salt, Sn salt, and aminecation salt, and n is 1.

In certain embodiments, when at least one monomer used to create thepolymer comprises the phosphono-phosphate group, said at least onemonomer has the structure of Formula 4:

-   -   wherein:        -   β is the site of attachment to the phosphono-phosphate group            of Formula 1;        -   R₈ is selected from the group consisting of —H and —CH₃;        -   L₁ is selected from the group consisting of a chemical bond,            arenediyl, and a structure of Formula 5:

-   -   wherein:        -   α is the site of attachment to the alkenyl radical in            Formula 4;        -   β is the site of attachment to the phosphono-phosphate group            of Formula 1;        -   X is selected from the group consisting of the structures in            Formulas 6-12;

-   -   wherein:        -   R₉ is selected from the group consisting of —H,            alkyl_((C1-8)), phosphonoalkyl, and            phosphono(phosphate)alkyl; and    -   Y is selected from the group consisting of alkanediyl,        alkoxydiyl, alkylaminodiyl and alkenediyl.

In certain embodiments, when at least one monomer used to create thepolymer comprises the phosphono-phosphate group and has the structure ofFormula 4, R₈ of Formula 4 is H. In certain embodiments, when at leastone monomer used to create the polymer comprises the phosphono-phosphategroup and has the structure of Formula 4, R₈ of Formula 4 is CH₃.

In certain embodiments, when at least one monomer used to create thepolymer comprises the phosphono-phosphate group, and said at least onemonomer has the structure of Formula 4, L₁ is a covalent bond. Inanother embodiment, when at least one monomer used to create the polymercomprises the phosphono-phosphate group, and said at least one monomerhas the structure of Formula 4, L₁ has the structure of Formula 5. Inanother embodiment, when at least one monomer used to create the polymercomprises the phosphono-phosphate group, said at least one monomer hasthe structure of Formula 4, and L₁ has the structure of Formula 5, thestructure of X is selected from the group consisting of Formula 6,Formula 9 and Formula 11. In another embodiment, when at least onemonomer used to create the polymer comprises the phosphono-phosphategroup, said at least one monomer has the structure of Formula 4, and L₁has the structure of Formula 5, X has the structure of of Formula 6. Inanother embodiment, when at least one monomer used to create the polymercomprises the phosphono-phosphate group, said at least one monomer hasthe structure of Formula 4, and L₁ has the structure of Formula 5, X hasthe structure of of Formula 7. In another embodiment, when at least onemonomer used to create the polymer comprises the phosphono-phosphategroup, said at least one monomer has the structure of Formula 4, and L₁has the structure of Formula 5, X has the structure of of Formula 9. Inanother embodiment, when at least one monomer used to create the polymercomprises the phosphono-phosphate group, said at least one monomer hasthe structure of Formula 4, and L₁ has the structure of Formula 5, X hasthe structure of of Formula 11. In another embodiment, when at least onemonomer used to create the polymer comprises the phosphono-phosphategroup, said at least one monomer has the structure of Formula 4, and L₁has the structure of Formula 5, X has the structure of of Formula 6 andY is alkanediyl. In another embodiment, when at least one monomer usedto create the polymer comprises the phosphono-phosphate group, said atleast one monomer has the structure of Formula 4, and L₁ has thestructure of Formula 5, X has the structure of of Formula 7 and Y isselected from the group consisting of alkanediyl and alkoxydiyl. Inanother embodiment, when at least one monomer used to create the polymercomprises the phosphono-phosphate group, said at least one monomer hasthe structure of Formula 4, and L₁ has the structure of Formula 5, X hasthe structure of of Formula 9 and Y is alkanediyl. In anotherembodiment, when at least one monomer used to create the polymercomprises the phosphono-phosphate group, said at least one monomer hasthe structure of Formula 4, and L₁ has the structure of Formula 5, X hasthe structure of of Formula 11 and Y is alkanediyl.

In certain embodiments, said anionic group is selected from the groupconsisting of phosphate, phosphonate, sulfate, sulfonate or carboxylate.In another embodiment, said anionic group is sulfonate. In anotherembodiment, said anionic group is carboxylate. In another embodiment,said anionic group is phosphonate.

In certain embodiments, when at least one monomer used to create thepolymer comprises an anionic group, said at least one monomer furthercomprises an alkenyl group of the structure of Formula 13:

-   -   wherein:        -   R₁₀ is selected from the group consisting of H or CH₃ and L₂            is a linking group to the anionic group.

In certain embodiments, when at least one monomer used to create thepolymer comprises an anionic group and said at least one monomer furthercomprises an alkenyl group of the structure of Formula 13, R₁₀ is H. Inanother embodiment, when at least one monomer used to create the polymercomprises an anionic group and said at least one monomer furthercomprises an alkenyl group of the structure of Formula 13, R₁₀ is CH₃.

In certain embodiments, when at least one monomer used to create thepolymer comprises an anionic group, said at least one monomer furthercomprises an alkenyl group of the structure of Formula 14:

-   -   wherein:        -   R₁₁ is selected from the group consisting of H and alkyl;        -   δ is the site of attachment to the anionic group;        -   L₃ is selected from a chemical bond, arenediyl, and a            structure of Formula 15;

-   -   wherein:        -   γ is the site of attachment to the alkenyl radical;        -   δ is the site of attachment to the anionic group;        -   W is selected from the structures in Formulas 16-22:

-   -   wherein:        -   R₁₂ is selected from the group consisting of —H and            alkyl_((C1-8)); and        -   V is selected from the group consisting of alkanediyl,            alkoxydiyl, alkylaminodiyl or alkenediyl.

In certain embodiments, when at least one monomer used to create thepolymer comprises an anionic group and said at least one monomer furthercomprises an alkenyl group of the structure of Formula 14, R₁₁ is H. Inanother embodiment, when at least one monomer used to create the polymercomprises an anionic group and said at least one monomer furthercomprises an alkenyl group of the structure of Formula 14, R₁₁ is CH₃.In another embodiment, when at least one monomer used to create thepolymer comprises an anionic group and said at least one monomer furthercomprises an alkenyl group of the structure of Formula 14, L₃ is acovalent bond. In another embodiment, when at least one monomer used tocreate the polymer comprises an anionic group and said at least onemonomer further comprises an alkenyl group of the structure of Formula14, R₁₁ is H and L₃ is a covalent bond. In another embodiment, when atleast one monomer used to create the polymer comprises an anionic groupand said at least one monomer further comprises an alkenyl group of thestructure of Formula 14, R₁₁ is CH₃ and L₃ is a covalent bond.

In certain embodiments, when at least one monomer used to create thepolymer comprises an anionic group and said at least one monomer furthercomprises an alkenyl group of the structure of Formula 14, L₃ has thestructure of Formula 15 and W has the structure of Formula 16. Inanother embodiment, when at least one monomer used to create the polymercomprises an anionic group and said at least one monomer furthercomprises an alkenyl group of the structure of Formula 14, L₃ has thestructure of Formula 15 and W has the structure of Formula 19. Inanother embodiment, when at least one monomer used to create the polymercomprises an anionic group and said at least one monomer furthercomprises an alkenyl group of the structure of Formula 14, L₃ has thestructure of Formula 15 and W has the structure of Formula 21. Incertain embodiments, when at least one monomer used to create thepolymer comprises an anionic group and said at least one monomer furthercomprises an alkenyl group of the structure of Formula 14, L₃ has thestructure of Formula 15 and W has the structure of Formula 16 and V isalkanediyl. In another embodiment, when at least one monomer used tocreate the polymer comprises an anionic group and said at least onemonomer further comprises an alkenyl group of the structure of Formula14, L₃ has the structure of Formula 15 and W has the structure ofFormula 19 and V is alkanediyl. In another embodiment, when at least onemonomer used to create the polymer comprises an anionic group and saidat least one monomer further comprises an alkenyl group of the structureof Formula 14, L₃ has the structure of Formula 15 and W has thestructure of Formula 21 and V is alkanediyl.

In certain embodiments, when at least one monomer used to create thepolymer comprises an anionic group, said at least one monomer isselected from the group consisting of vinyl phosphonate, vinylsulfonate, acrylate, methyl vinyl phosphonate, methyl vinyl sulfonate,methacrylate, styrene phosphonate, styrene sulfonate, vinyl benzenephosphonate, vinyl benzene sulfonate, 2-acrylamido-2-methyl propanesulfonate (AMPS), and 2-Sulfopropyl Acrylate (SPA).

In certain embodiments, when at least one monomer used to create saidpolymer comprises said anionic group and at least one monomer used tocreate said polymer comprises said phosphono-phosphate group, the ratioof said at least one monomer comprising said phosphono-phosphate groupto said at least one monomer comprising said anionic group ranges from99.9:0.1 to 0.1:99.9, respectively.

In certain embodiments, when at least one monomer used to create saidpolymer comprises said anionic group and at least one monomer used tocreate said polymer comprises said phosphono-phosphate group, the ratioof said at least one monomer comprising said phosphono-phosphate groupto said at least one monomer comprising said anionic group ranges from99:1 to 1:99, respectively.

In certain embodiments, when at least one monomer used to create saidpolymer comprises said anionic group and at least one monomer used tocreate said polymer comprises said phosphono-phosphate group, the ratioof said at least one monomer comprising said phosphono-phosphate groupto said at least one monomer comprising said anionic group ranges from90:10 to 10:90, respectively.

In certain embodiments, when at least one monomer used to create saidpolymer comprises said anionic group and at least one monomer used tocreate said polymer comprises said phosphono-phosphate group, the ratioof said at least one monomer comprising said phosphono-phosphate groupto said at least one monomer comprising said anionic group ranges from70:30 to 30:70, respectively.

Another embodiment of the present invention is an oral care compositioncomprising polymer which in this context is meant to include oligomerssuch as dimers trimers and tetramers. The polymer includes aphosphono-phosphate group and an anionic group with the structure ofFormula 23:

-   -   wherein:        -   R₁ is selected from the group consisting of —H, alkyl,            alkanediyl-alkoxy, metal salt having Na, K, Ca, Mg, Mn, Zn,            Fe, or Sn cation, amine cation salt, and a structure of            Formula 2:

-   -   -   -   wherein:            -   θ is the site of attachment to Formula 23,            -   R₄ and R₅ are independently selected from the group                consisting of —H, alkyl, alkanediyl-alkoxy, metal salt                having Na, K, Ca, Mg, Mn, Zn, Fe, or Sn cation, and                amine cation salt;

        -   R₂ is selected from the group consisting of —H, alkyl,            alkanediyl-alkoxy, metal salt having Na, K, Ca, Mg, Mn, Zn,            Fe, or Sn cation, amine cation salt, and a structure of            Formula 3:

-   -   -   -   wherein:            -   θ is the site of attachment to Formula 23,            -   R₆, and R₇ are independently selected from the group                consisting of —H, alkyl, alkanediyl-alkoxy, metal salt                having Na, K, Ca, Mg, Mn, Zn, Fe, or Sn cation, and                amine cation salt, and            -   n is an integer from 1 to 22; and

        -   R₃ is selected from the group consisting of —H, alkyl,            alkanediyl-alkoxy, metal salt having Na, K, Ca, Mg, Mn, Zn,            Fe, or Sn cation, and amine cation salt,

        -   and said anionic group is covalently bound to the polymer            backbone, side group, or side chain and is selected from the            chemical group consisting of phosphate, phosphonate,            phosphinate, sulfate, sulfonate, sulfinate, mercapto,            carboxylate, hydroxyamino, amine oxide, and hydroxamate.

        -   R₈ is selected from the group consisting of —H and —CH₃;

        -   L₁ is selected from the group consisting of a chemical bond,            arenediyl, and a structure of Formula 5:

-   -   -   -   wherein:                -   α is the site of attachment to the polymer backbone;                -   β is the site of attachment to the                    phosphono-phosphate;                -   X is selected from the group consisting of the                    structures in Formulas 6-12;

-   -   -   -   wherein:                -   R₉ is selected from the group consisting of —H,                    alkyl_((C1-8)), phosphonoalkyl, and                    phosphono(phosphate)alkyl; and                -   Y is selected from the group consisting of                    alkanediyl, alkoxydiyl, alkylaminodiyl and                    alkenediyl,

        -   R₁₁ is selected from the group consisting of —H and —CH₃;

        -   δ is the site of attachment to the anionic group;

        -   L₃ is selected from a chemical bond, arenediyl, and a            structure of Formula 15;

-   -   -   wherein:            -   γ is the site of attachment to the polymer backbone;            -   δ is the site of attachment to the anionic group;            -   W is selected from the structures in Formulas 16-22:

-   -   -   wherein:            -   R₁₂ is selected from the group consisting of —H and                alkyl_((C1-8)); and            -   V is selected from the group consisting of alkanediyl,                alkoxydiyl, alkylaminodiyl or alkenediyl;        -   R₁₃ is a chemical group resulting from polymer initiation;        -   R₁₄ is a chemical group resulting chain termination;        -   m is an integer from 2 to 450; and        -   p is an integer from 2 to 450.

In one embodiment of the polymer, R₁, R₂, and R₃ are independentlyselected from the group consisting of H, Na salt, and K salt. In oneembodiment of the polymer, R₁, R₂, and R₃ are independently selectedfrom the group consisting of H, Na salt, K salt, Zn salt, Ca salt, Snsalt, and amine cation salt.

In another embodiment of the polymer, R₁ has the structure of Formula 2.In a further embodiment of the polymer, R₁ has the structure of Formula2 and R₄ and R₅ are independently selected from the group consisting ofH, Na salt, and K salt. In a further embodiment of the polymer, R₁ hasthe structure of Formula 2 and R₄ and R₅ are independently selected fromthe group consisting of —H, Na salt, K salt, Zn salt, Ca salt, Sn salt,and amine cation salt.

In another embodiment of the polymer, R₂ has the structure of Formula 3.In another embodiment of the polymer R₂ has the structure of Formula 3and n is an integer from 1 to 3. In another embodiment of the polymer,R₂ has the structure of Formula 3 and n is 1. In another embodiment ofthe polymer, R₂ has the structure of Formula 3 and R₆ and R₇ areindependently selected from the group consisting of H, Na salt, and Ksalt. In another embodiment of the polymer, R₂ has the structure ofFormula 3 and R₆ and R₇ are independently selected from the groupconsisting of H, Na salt, K salt, Zn salt, Ca salt, Sn salt, and aminecation salt. In another embodiment of the compound, R₂ has the structureof Formula 3, R₆ and R₇ are independently selected from the groupconsisting of H, Na salt, K salt, Zn salt, Ca salt, Sn salt, and aminecation salt, and n is 1.

In one embodiment of the polymer, R₈ is H. In another embodiment, R₈ isCH₃.

In one embodiment of the polymer, L₁ is a covalent bond. In anotherembodiment, L₁ has the structure of Formula 5. In another embodiment L₁has the structure of Formula 5, the structure of X is selected from thegroup consisting of Formula 6, Formula 9 and Formula 11. In anotherembodiment, L₁ has the structure of Formula 5, X has the structure ofFormula 6. In another embodiment, L₁ has the structure of Formula 5, Xhas the structure of Formula 7. In another embodiment, L₁ has thestructure of Formula 5, X has the structure of Formula 9. In anotherembodiment, L₁ has the structure of Formula 5, X has the structure ofFormula 11. In another embodiment, L₁ has the structure of Formula 5, Xhas the structure of Formula 6 and Y is alkanediyl. In anotherembodiment, L₁ has the structure of Formula 5, X has the structure ofFormula 7 and Y is selected from the group consisting of alkanediyl andalkoxydiyl. In another embodiment, L₁ has the structure of Formula 5, Xhas the structure of of Formula 9 and Y is alkanediyl. In anotherembodiment, L₁ has the structure of Formula 5, X has the structure ofFormula 11 and Y is alkanediyl.

In one embodiment of the polymer, said anionic group is selected fromthe group consisting of phosphate, phosphonate, sulfate, sulfonate orcarboxylate. In another embodiment, said anionic group is sulfonate. Inanother embodiment, said anionic group is carboxylate. In anotherembodiment, said anionic group is phosphonate.

In one embodiment of the polymer, R₁₁ is H. In another embodiment, R₁₁is CH₃. In another embodiment, L₃ is a covalent bond. In anotherembodiment, R₁₁ is H and L₃ is a covalent bond. In another embodiment,R₁₁ is CH₃ and L₃ is a covalent bond.

In one embodiment, L₃ has the structure of Formula 15 and W has thestructure of Formula 16. In another embodiment, L₃ has the structure ofFormula 15 and W has the structure of Formula 19. In another embodiment,L₃ has the structure of Formula 15 and W has the structure of Formula21. In one embodiment, L₃ has the structure of Formula 15 and W has thestructure of Formula 16 and V is alkanediyl. In another embodiment, L₃has the structure of Formula 15 and W has the structure of Formula 19and V is alkanediyl. In another embodiment, L₃ has the structure ofFormula 15 and W has the structure of Formula 21 and V is alkanediyl.

In one embodiment of the polymer, R₁₃, the chemical group resulting frompolymer initiation, is selected from the structures of Formula 24-28:

-   -   wherein:        -   R₁₅ is selected from the group consisting of —H, Na, K and            amine cation salt;        -   τ is the site of attachment to polymer backbone and;        -   Q is the non-olefin residue of a monomer used in            polymerization.

In a further embodiment, Q has the structure of Formula 29:

-   -   wherein: L₁, R₁, R₂ and R₃ are as previously noted and K denotes        the site of attachment to Formula 28.

In a further embodiment of the polymer, Q has the structure of Formula30:

-   -   wherein: L₃, and δ are as previously noted and x denotes the        site of attachment to Formula 28.

In a further embodiment, Q is phosphono-phosphate. In a furtherembodiment Q is sulfonate. In a further embodiment Q is phosphonate.

In one embodiment of the polymer, R₁₄, the chemical group resulting frompolymer termination, is selected from the group consisting of —H. In oneembodiment of the compound, R₁₄, the chemical group resulting frompolymer termination, is another polymer chain with a head to headattachment.

In one preferred embodiment of the polymer, R₁, R₂, and R₃ areindependently selected from the group consisting of H, Na salt, K saltand amine cation salt, R₈ is H, L₁ is a covalent bond, L₃ is a covalentbond, the anionic group is sulfonate, R₁₃ is the structure of Formula28, Q is the structure of Formula 29 or Formula 30 and R₁₄ is H.

Methods of Making the Polymers

Embodiments of the present invention can be made using these generalfollowing methods. The polymers of the present invention can be made bya wide variety of techniques, including bulk, solution, emulsion, orsuspension polymerization. Polymerization methods and techniques forpolymerization are described generally in Encyclopedia of PolymerScience and Technology, Interscience Publishers (New York), Vol. 7, pp.361-431 (1967), and Kirk-Othmer Encyclopedia of Chemical Technology, 3rdedition, Vol 18, pp. 740-744, John Wiley & Sons (New York), 1982, bothincorporated by reference herein. See also Sorenson, W. P. and Campbell,T. W., Preparative Methods of Polymer Chemistry. 2nd edition,Interscience Publishers (New York), 1968, pp. 248-251, incorporated byreference herein, for general reaction techniques suitable for thepresent invention. In one example, the polymers are made by free radicalcopolymerization, using water soluble initiators. Suitable free radicalinitiators include, but are not limited to, thermal initiators, redoxcouples, and photochemical initiators. Redox and photochemicalinitiators may be used for polymerization processes initiated attemperatures below about 30° C. Such initiators are described generallyin Kirk-Othmer Encyclopedia of Chemical Technology, 3rd edition, JohnWiley & Sons (New York), Vol. 13, pp. 355-373 (1981), incorporated byreference herein. Typical water soluble initiators that can provideradicals at 30° C. or below include redox couples, such as potassiumpersulfate/silver nitrate, and ascorbic acid/hydrogen peroxide. In oneexample, the method utilizes thermal initiators in polymerizationprocesses conducted above 40° C. Water soluble initiators that canprovide radicals at 40° C. or higher can be used. These include, but arenot limited to, hydrogen peroxide, ammonium persulfate, and2,2′-azobis(2-amidinopropane) dihydrochloride. In one example, watersoluble starting monomers are polymerized in a water at 60° C. usingammonium persulfate as the initiator.

The identity of chemical functional groups at the terminal ends of alinear polymer depend upon how the polymerization of that polymer chainwas initiated and terminated. For free radical polymerization, any freeradical in the system can begin a new chain. This free radical can be adirect derivative of the initiator such as a sulfate radical frompersulfate, or alkyl radical from the azo type initiators (such as butnot limited to 2,2′azobis(2-amidinopropane) dihydrochloride). The freeradical can also be the result of a transfer reaction, for instancebetween a water and another radical to produce a hydroxyl radical orbetween a phosphate and another radical to produce a phosphate radical.Non-limiting examples of these resulting structures are given below,where R represents an H or appropriate counter ion such as Na, K or anamine and τ represents the site of attachment to the polymer.

The free radical can also be the result of a chain transfer reaction,where the radical is transferred from a growing polymer chain to start anew chain. Chain transfer has been explicitly noted in polymerization ofvinyl phosphonate monomers. Bingöl et al. Macromolecules 2008, 41,1634-1639), incorporated by reference herein, describe howpolymerization of alkyl esters of vinyl phosphonate result in chaintransfer on the alkyl group. This transfer ultimately begins a newpolymer chain with an olefin containing chemical group on the initiatingend. A similar phenomenon appears to happen with vinylphosphono-phosphate based polymerizations. A chain transfer stops growthof one chain and begins a new chain.

In the phosphono-phosphate containing polymers, vinyl CH₂ groups wereobserved in the final polymers compositions. These vinyl groups arehypothesized to form from one of two mechanisms. The first mechanism isa similar phenomenon to that observed by Bingöl, unlike Bingöl, however,the olefin is not from the alkyl ester of phoshonate, but potentiallyfrom the vinyl monomer on the newly initiated chain. Not wanting to bebound by theory, the below scheme is given as a possible route by whichchain transfer could result in an olefin at the site of initiation for ageneric free radical polymerizable monomer where the non-olefin portionof the monomer is simply depicted as Q for clarity. Q can represent anynumber of chemical functional groups and is not limited to a singlechemical entity. Olefin terminated groups based on vinyl phosphonate andvinyl phosphono-phosphate have been observed.

The second mechanism to introduce vinyl groups involves a backbitingreaction and beta scission. This mechanism has been extensively notedfor acrylate polymers in the literature. A vinyl group and primaryradical result after beta scission.

Using the previously used nomenclature of using τ to represent the siteof attachment to the polymer, the initial functional group can bewritten as follows. It should be noted that both the chain transfer andbackbiting followed by beta scission mechanisms will produce a vinylgroup with two protons on the same carbon atom.

The chemical group on the terminating end of the polymer chain dependsupon how the chain is terminated. The most common terminations are thepreviously mentioned chain transfer, and backbiting reactions as well ascombination and disproportionation. In chain transfer and backbiting,the terminating group is typically a hydrogen. In combination, thepropagating radicals on two chains react to form a new chain. Thisreaction causes a “head to head” configuration at the point ofattachment.

In disproportionation, a hydrogen is exchanged from one radical chain toanother radical chain. The result is one chain is unsaturated while theother is saturated. Of note, the resulting unsaturated group is not avinyl group. Each carbon in the unsaturation has only one hydrogen.

A polymer comprising a phosphono-phosphate group and anionic group canhave the phosphono-phosphate and anionic groups attached directly offthe polymer backbone, on a side group, or on a side chain. Thisphosphono-phosphate group can be incorporated into the polymer by eitherpolymerization of monomers having the phosphono-phosphate group, or bypolymerization of monomers without a phosphono-phosphate group andsubsequent post-polymerization modification of the resulting polymer toadd the phosphono-phosphate group. Similarly, the anionic group can beincorporated into the polymer by either polymerization of monomershaving the anionic group, or by polymerization of monomers without ananionic group and subsequent post-polymerization modification of theresulting polymer to add the anionic group. The examples in thesubsequent paragraphs will depict different methods of incorporatingphosphono-phosphate groups onto polymers with the anionic group eitherintroduced as a co-monomer or as a result of incomplete reaction of aphosphonate when attempting to form a phosphono-phosphate group. Thissection will not depict all possible anionic monomers, nor will itdepict the various methods of introducing anionic groups onto a polymerafter polymerization, since they are well known to those skilled in theart.

As examples of polymers comprising a phosphono-phosphate group attachedto a polymer backbone, consider the polymers made from the monomersvinyl phosphonate or methyl-vinyl phosphonate. Vinyl phosphonate ormethyl-vinyl phosphonate can be chemically reacted to formphosphono-phosphate monomers as shown in reaction 1 in Scheme 1. Thesephosphono-phosphate containing monomers can then be co-polymerized witha monomer containing an anionic group as shown in reaction 2 of the samescheme to yield a phosphono-phosphate containing polymer with thephosphono-phosphate group attached directly to the polymer backbone.Alternatively, vinyl phosphonate or methyl-vinyl phosphonate can befirst co-polymerized as shown in reaction 3 to yield a polymer. Afterpolymerization, the phosphono-phosphate group can be created bypost-polymerization modification by reacting the attached phosphonatemoiety as shown in reaction 4 thus creating a phosphono-phosphate groupattached directly to the polymer backbone.

A second manner of creating a phosphono-phosphate group and anionicgroup attached directly to the backbone by a post polymerizationmodification can be exemplified by starting with polyethylene. For anexample of the first reaction in such a modification, see M. Anbar, G.A. St. John and A. C Scott, J Dent Res Vol 53, No 4, pp 867-878, 1974.As shown in Scheme 2, polyethylene is first phosphorylated oxidativelywith oxygen and PCl₃ to form a randomly phosphonated polymer. Thisphosphonated polymer can then be modified to produce a randomlysubstituted phosphono-phosphate/phosphonate polymer. The reactionproducts shown are meant to show the random nature of the points ofattachment of the phosphonate and phosphono-phosphate groups of theresulting polymer. Phosphonate groups are anionic.

As an example of the production of polymers having a phosphono-phosphategroup attached to a side group, consider the vinyl benzyl chemistrydepicted in Scheme 3. 4-Vinylbenzyl chloride can be reacted with diethylphosphite to form vinyl benzyl phosphonate depicted in reaction 1 ofScheme 3. For an example of this reaction, see Frantz, Richard; Durand,Jean-Olivier; Carre, Francis; Lanneau, Gerard F.; Le Bideau, Jean;Alonso, Bruno; Massiot, Dominique, Chemistry—A European Journal, Volume9, Issue 3, pp. 770-775, 2003. Vinyl benzyl phosphonate can be reactedto form vinyl benzyl phosphono-phosphate shown in reaction 2, asdescribed in the example section below. This monomer can then beco-polymerized, to form a phosphono-phosphate and anionic containingpolymer depicted by reaction 5, in which the phosphono-phosphate groupis attached to a side group on the polymer. Alternatively, the firstintermediate, vinyl benzyl phosphonate, can be polymerized shown inreaction 4 to make a polymer with vinyl benzyl phosphonate. For anexample of this reaction, see M. Anbar, G. A. St. John and A. C Scott, JDent Res Vol 53, No 4, pp 867-878, 1974. The polymer with vinyl benzylphosphonate can then be reacted as shown in reaction 7 to produce aphosphono-phosphate and anionic containing polymer where thephosphono-phosphate group is attached to a side group on the polymer bya post polymerization modification. A second route involving a postpolymerization modification is also shown in the same scheme.4-Vinylbenzyl chloride can be co-polymerized to provide a polymer withvinyl benzyl chloride shown in reaction 3. This polymer can bephosphonated shown in reaction 6 (for example, see Sang Hun Kim, YoungChul Park, Gui Hyun Jung, and Chang Gi Cho, Macromolecular Research Vol15 No 6 pp 587-597, 2007), and then the resulting polymer vinyl benzylphosphonate reacted to produce the phosphono-phosphate and anioniccontaining polymer shown in reaction 7.

As a first example of polymers comprising a phosphono-phosphate groupattached to a side chain, consider the poly ethylene glycol (PEG) sidechains depicted in Scheme 4. A phosphonate containing PEG chain can bereacted with acryl chloride to produce an acrylic ester with an PEGterminated phosphonate. After reaction to produce a phosphono-phosphate,the phosphono-phosphate monomer can be co-polymerized with an anioniccontaining monomer to produce a phosphono-phosphate and anioniccontaining polymer where the phosphono-phosphate is attached to a sidechain of the polymer.

As a second example of polymers comprising a phosphono-phosphate groupattached to a side chain, consider the poly vinyl alcohol depicted inScheme 5. The hydroxyl groups can be reacted with ethylene oxide toproduce a polymer with PEG side chains. The terminating hydroxy on theside chains can be reacted with vinyl phosphonate, and then partiallyreacted to form a phosphono-phosphate/phosphonate polymer. This examplethus depicts a phosphono-phosphate containing polymer where thephosphono-phosphate is attached to a side chain of the polymer and isadded via a post polymerization modification. Phosphonate is an anionicgroup.

The schemes depicted are not meant to be exhaustive in nature, but aremeant to convey the various manners in which phosphono-phosphate andanionic containing polymers may be produced. The examples provide bothtechnical details for synthesis and numerous variations of polymerscontaining phosphono-phosphate and anionic groups, including polymerswith phosphono-phosphate groups attached directly to the polymerbackbone and polymers with phosphono-phosphate groups attached to sidegroups. For further examples of phosphonate containing monomers andpolymers that can be transformed into phosphono-phosphonate containingmonomers and polymers, see Sophie Monge, Benjamin Canniccioni, GhislainDavid and Jean-Jacques Robin, RSC Polymer Chemistry Series No. 11,Phosphorus-Based Polymers: From Synthesis to Applications, Edited bySophie Monge and Ghislain David, The Royal Society of Chemistry 2014,Published by the Royal Society of Chemistry, www.rsc.org.Uses of the Phosphono-Phosphate Containing Polymers

The phosphono-phosphate containing polymers according to the presentinvention can be incorporated into a variety of compositions. Thesecompositions include both aqueous and non-aqueous compositions. Thecompositions are useful for treating teeth, hair, body, fabric, paper,non-wovens and hard surfaces. The compositions find utility in watertreatments, boiler treatments, treating ship hulls, oil wells,batteries, baking, leavening, ceramics, plastics stabilizers, glassmanufacture, cheese production, buffers in food, abrasives indentifrice, binders in meat, coffee creamers, antifreeze, dispersingagents in paints liquid soaps, metal cleaners synthetic rubber, textilesand flame retardants. The compositions are also useful for treatingmaterials containing multivalent metal cations including but not limitedto calcium, tin, magnesium and iron. Examples of such materials includehydroxyapatite, calcium carbonate (amorphous, calcite, aragonite),calcium phosphate, calcium hydroxide, magnesium carbonate, magnesiumphosphate, soap scum (mixture of calcium, magnesium, and iron salts ofstearic acid and carbonate), and hard water stains. In certainembodiments, the composition comprising phosphono-phosphate containingpolymers is non-aqueous. In another embodiment, the composition isaqueous.

The phosphono-phosphate containing compounds and polymers can be appliedto a variety of substrates. Embodiments of substrates include biologicalmaterial, fabric, non-woven materials, paper products and hard surfacematerials. In certain embodiments, the biological material comprisesteeth. In another embodiment, the biological material comprises keratin,such as hair or skin.

Oral Care Compositions

The present invention further relates to oral care compositionscomprising the polymers of the present invention comprising aphosphono-phosphate group and anionic group. The oral care compositionsof the present invention can further comprise additional ingredientssuch as polymeric mineral surface agent agents, metal ion salts, water,humectants, fluoride source, buffering agents, anticalculus agents,abrasive polishing materials, thickening agents, surfactants, titaniumdioxide, colorants, flavorants, antimicrobial agents, and mixturesthereof.

A preferred polymeric mineral surface active agent is a polyphosphate. Apolyphosphate is generally understood to consist of two or morephosphate molecules arranged primarily in a linear configuration,although some cyclic derivatives may be present. Although pyrophosphatesare technically polyphosphates, the polyphosphates desired are thosehaving around three or more phosphate molecules so that surfaceadsorption at effective concentrations produces sufficient non-boundphosphate functions, which enhance the anionic surface charge as well ashydrophilic character of the surfaces. The pyrophosphates are discussedseparately under additional anticalculus agents. The inorganicpolyphosphate salts desired include tripolyphosphate, tetrapolyphosphateand hexametaphosphate, among others. Polyphosphates larger thantetrapolyphosphate usually occur as amorphous glassy materials.Preferred in this invention are the linear “glassy” polyphosphateshaving the formula:XO(XPO₃)_(n)Xwherein X is sodium or potassium and n averages from about 3 to about125. Preferred polyphosphates are those having n averaging from about 6to about 21, such as those manufactured by FMC Corporation andcommercially known as Sodaphos (n≈6), Hexaphos (n≈13), and Glass H(n≈21). A particularly preferred polyphosphate has n averaging about 21such as Glass H. These polyphosphates may be used alone or in acombination thereof.

Oral compositions which comprise polyphosphates are disclosed in e.g.,U.S. Pat. Nos. 5,939,052, 6,190,644, 6,187,295, and 6,350,436, allassigned to The Procter & Gamble Co. In these compositions, thepolyphosphates are disclosed to provide benefits including tartarinhibition and reducing aesthetic negatives such as astringency andstaining caused by other actives such as stannous. The use ofpolyphosphates for the prevention of dental erosion is not disclosed.The polyphosphate sources are also described in more detail inKirk-Othmer Encyclopedia of Chemical Technology, Fourth Edition, Volume18, Wiley-Interscience Publishers (1996). An effective amount of apolymeric mineral surface active agent will typically be from about 1%to about 35%, preferably from about 2% to about 30%, more preferablyfrom about 5% to about 25%, and most preferably from about 6% to about20%, by weight of the total oral composition.

The metal ions suitable for use in the present invention have strongaffinity for enamel surface and include stannous, copper and zinc ions.These ions provide surface protection effects by reacting with toothsurface ions and/or other components of the composition to producehighly insoluble compounds on the surface. Additionally, these metalions undergo oxidation and hydrolysis under salivary pH conditions andproduce insoluble deposits on tooth surfaces. The present compositionsmay comprise a metal ion source that provides stannous ions, zinc ions,copper ions, or mixtures thereof. The metal ion source can be a solubleor a sparingly soluble compound of stannous, zinc, or copper withinorganic or organic counter ions. Examples include the fluoride,chloride, chlorofluoride, acetate, hexafluorozirconate, sulfate,tartrate, gluconate, citrate, malate, glycinate, pyrophosphate,metaphosphate, oxalate, phosphate, carbonate salts and oxides ofstannous, zinc, and copper. Preferred are stannous salts, such asstannous fluoride or stannous chloride.

Stannous, zinc and copper ions have been found to help in the reductionof gingivitis, plaque, sensitivity, and improved breath benefits.Dentifrices containing stannous salts, particularly stannous fluorideand stannous chloride, are described in U.S. Pat. No. 5,004,597 toMajeti et al. Other descriptions of stannous salts are found in U.S.Pat. No. 5,578,293 issued to Prencipe et al. and in U.S. Pat. No.5,281,410 issued to Lukacovic et al.

The combined metal ion source(s) will be present in an amount of fromabout 0.1% to about 11%, by weight of the final composition. Preferably,the metal ion sources are present in an amount of from about 0.5 toabout 7%, more preferably from about 1% to about 5%. Preferably, thestannous salts may be present in an amount of from about 0.1 to about7%, more preferably from about 1% to about 5%, and most preferably fromabout 1.5% to about 3% by weight of the total composition.

In preparing the present compositions, it is desirable to water and/orhumectants to the compositions. Another optional component of thecompositions desired herein is a humectant. The humectant serves to keeptoothpaste compositions from hardening upon exposure to air and certainhumectants can also impart desirable sweetness of flavor to toothpastecompositions. Suitable humectants for use in the invention includeglycerin, sorbitol, polyethylene glycol, propylene glycol, and otheredible polyhydric alcohols. The humectant generally comprises from about0% to 70%, and preferably from about 15% to 55%, by weight of thecomposition.

Water will generally comprise from about 5% to about 70%, and preferablyfrom about 10% to about 50%, by weight of the composition herein.Generally, the level of water is up to about 50%, preferably from about5% to about 30%, and more preferably from about 10% to about 25%, byweight of the oral composition. The amounts of water include the freewater which is added plus that which is introduced with other materials,such as with sorbitol, silica, surfactant solutions, and/or colorsolutions.

The oral composition of the present invention may incorporate a solublefluoride source capable of providing free fluoride ions. The fluorideion source may preferably be in a separate phase than the polymericsurface active agent to aid in stability. Preferred soluble fluoride ionsources include sodium fluoride, stannous fluoride, indium fluoride,amine fluoride and sodium monofluorophosphate. Sodium fluoride andstannous fluoride the most preferred soluble fluoride ion source.Stannous fluoride and methods of stabilization are described in U.S.Pat. No. 5,004,597 issued to Majeti et al. and in U.S. Pat. No.5,578,293 issued to Prencipe et al., in addition to other sources Norriset al., U.S. Pat. No. 2,946,725, issued Jul. 26, 1960, and Widder etal., U.S. Pat. No. 3,678,154 issued Jul. 18, 1972, disclose suchfluoride ion sources as well as others.

The present compositions may contain a buffering agent. Bufferingagents, as used herein, refer to agents that can be used to adjust thepH of the compositions to a range of about pH 4 to about pH 10. The oralcomposition containing a polymeric mineral surface active agent willtypically have a slurry pH of from about 4 to about 10, preferably fromabout 4.5 to about 8, and more preferably from about 5.5 to about 7. Thebuffering agents include alkali metal hydroxides, carbonates,sesquicarbonates, borates, silicates, phosphates, imidazole, andmixtures thereof. Specific buffering agents include monosodiumphosphate, trisodium phosphate, sodium hydroxide, potassium hydroxide,alkali metal carbonate salts, sodium carbonate, imidazole, pyrophosphatesalts, citric acid, and sodium citrate. Buffering agents are used at alevel of from about 0.1% to about 30%, preferably from about 1% to about10%, and more preferably from about 1.5% to about 3%, by weight of thepresent composition.

Pyrophosphate salts may be used in the present invention as anticalculusagents. The pyrophosphate salts useful in the present compositionsinclude the dialkali metal pyrophosphate salts, tetra alkali metalpyrophosphate salts, and mixtures thereof. Disodium dihydrogenpyrophosphate (Na₂H₂P₂O₇), tetrasodium pyrophosphate (Na₄P₂O₇), andtetrapotassium pyrophosphate (K₄P₂O₇) in their unhydrated as well ashydrated forms are the preferred species. The amount of pyrophosphatesalt useful in making these compositions is any tartar control effectiveamount, and is generally from about 1.5% to about 15%, preferably fromabout 2% to about 10%, and most preferably from about 2.5% to about 8%,by weight of the composition. The pyrophosphate salts are described inmore detail in Kirk-Othmer Encyclopedia of Chemical Technology, ThirdEdition, Volume 17, Wiley-Interscience Publishers (1982).

An abrasive polishing material may also be included in the oralcompositions. The abrasive polishing material contemplated for use inthe compositions of the present invention can be any material which doesnot excessively abrade dentin. The abrasive polishing material should beformulated in the oral composition so that it does not compromise thestability of any ingredients, such as stannous fluoride. Typicalabrasive polishing materials include silica gels and precipitates;aluminas; phosphates including orthophosphates, polymetaphosphates, andpyrophosphates; and mixtures thereof. Specific examples includedicalcium orthophosphate dihydrate, calcium pyrophosphate, tricalciumphosphate, calcium polymetaphosphate, insoluble sodiumpolymetaphosphate, hydrated alumina, beta calcium pyrophosphate, calciumcarbonate, and resinous abrasive materials such as particulatecondensation products of urea and formaldehyde, and others such asdisclosed by Cooley et al in U.S. Pat. No. 3,070,510, issued Dec. 25,1962. Mixtures of abrasives may also be used. Silica dental abrasives ofvarious types are preferred because of their unique benefits ofexceptional dental cleaning and polishing performance without undulyabrading tooth enamel or dentine. The abrasive in the toothpastecompositions described herein is generally present at a level of fromabout 6% to about 70% by weight of the composition. Preferably,toothpastes contain from about 10% to about 50% of abrasive, by weightof the dentifrice composition.

The present invention may also include an alkali metal bicarbonate salt.Alkali metal bicarbonate salts are soluble in water and unlessstabilized, tend to release carbon dioxide in an aqueous system. Sodiumbicarbonate, also known as baking soda, is the preferred alkali metalbicarbonate salt. The alkali metal bicarbonate salt also functions as abuffering agent. The present composition may contain from about 0.5% toabout 50%, preferably from about 0.5% to about 30%, more preferably fromabout 2% to about 20%, and most preferably from about 5% to about 18% ofan alkali metal bicarbonate salt, by weight of the dentifricecomposition.

The present invention provides compositions in the form of toothpastes,dentifrices, tooth powder, topical oral gels, mouthrinses, dentureproduct, mouthsprays, lozenges, oral tablets, and chewing gums.Typically these compositions will contain some thickening material orbinders to provide a desirable consistency. Preferred thickening agentsare carboxyvinyl polymers, carrageenan, hydroxyethyl cellulose, andwater soluble salts of cellulose ethers such as sodiumcarboxymethylcellulose and sodium hydroxyethyl cellulose. Natural gumssuch as gum karaya, xanthan gum, gum arabic, and gum tragacanth can alsobe used. Colloidal magnesium aluminum silicate or finely divided silicacan be used as part of the thickening agent to further improve texture.Thickening agents can be used in an of amount from about 0.1% to about15%, by weight of the dentifrice composition.

The present compositions may also comprise surfactants, also commonlyreferred to as sudsing agents. Suitable surfactants are those which arereasonably stable and foam throughout a wide pH range. The surfactantmay be anionic, nonionic, amphoteric, zwitterionic, cationic, ormixtures thereof. Anionic surfactants useful herein include thewater-soluble salts of alkyl sulfates having from 8 to 20 carbon atomsin the alkyl radical (e.g., sodium alkyl sulfate) and the water-solublesalts of sulfonated monoglycerides of fatty acids having from 8 to 20carbon atoms. Sodium lauryl sulfate and sodium coconut monoglyceridesulfonates are examples of anionic surfactants of this type. Othersuitable anionic surfactants are sarcosinates, such as sodium lauroylsarcosinate, taurates, sodium lauryl sulfoacetate, sodium lauroylisethionate, sodium laureth carboxylate, and sodium dodecylbenzenesulfonate. Mixtures of anionic surfactants can also be employed.Many suitable anionic surfactants are disclosed by Agricola et al., U.S.Pat. No. 3,959,458, issued May 25, 1976. Nonionic surfactants which canbe used in the compositions of the present invention can be broadlydefined as compounds produced by the condensation of alkylene oxidegroups (hydrophilic in nature) with an organic hydrophobic compoundwhich may be aliphatic or alkyl-aromatic in nature. Examples of suitablenonionic surfactants include poloxamers (sold under trade namePluronic), polyoxyethylene, polyoxyethylene sorbitan esters (sold undertrade name Tweens), fatty alcohol ethoxylates, polyethylene oxidecondensates of alkyl phenols, products derived from the condensation ofethylene oxide with the reaction product of propylene oxide and ethylenediamine, ethylene oxide condensates of aliphatic alcohols, long chaintertiary amine oxides, long chain tertiary phosphine oxides, long chaindialkyl sulfoxides, and mixtures of such materials. The amphotericsurfactants useful in the present invention can be broadly described asderivatives of aliphatic secondary and tertiary amines in which thealiphatic radical can be a straight chain or branched and wherein one ofthe aliphatic substituents contains from about 8 to about 18 carbonatoms and one contains an anionic water-solubilizing group, e.g.,carboxylate, sulfonate, sulfate, phosphate, or phosphonate. Othersuitable amphoteric surfactants are betaines, specificallycocamidopropyl betaine. Mixtures of amphoteric surfactants can also beemployed. Many of these suitable nonionic and amphoteric surfactants aredisclosed by Gieske et al., U.S. Pat. No. 4,051,234, issued Sep. 27,1977. The present composition typically comprises one or moresurfactants each at a level of from about 0.25% to about 12%, preferablyfrom about 0.5% to about 8%, and most preferably from about 1% to about6%, by weight of the composition.

Titanium dioxide may also be added to the present composition. Titaniumdioxide is a white powder which adds opacity to the compositions.Titanium dioxide generally comprises from about 0.25% to about 5%, byweight of the composition.

Coloring agents may also be added to the present composition. Thecoloring agent may be in the form of an aqueous solution, preferably 1%coloring agent in a solution of water. Color solutions generallycomprise from about 0.01% to about 5%, by weight of the composition.

A flavor system can also be added to the compositions. Suitableflavoring components include oil of wintergreen, oil of peppermint, oilof spearmint, clove bud oil, menthol, anethole, methyl salicylate,eucalyptol, cassia, 1-menthyl acetate, sage, eugenol, parsley oil,oxanone, alpha-irisone, marjoram, lemon, orange, propenyl guaethol,cinnamon, vanillin, ethyl vanillin, heliotropine, 4-cis-heptenal,diacetyl, methyl-para-tert-butyl phenyl acetate, xylitol, and mixturesthereof. Coolants may also be part of the flavor system. Preferredcoolants in the present compositions are the paramenthan carboxyamideagents such as N-ethyl-p-menthan-3-carboxamide (known commercially as“WS-3”) and mixtures thereof. A flavor system is generally used in thecompositions at levels of from about 0.001% to about 5%, by weight ofthe composition.

The present invention may also include other agents, such asantimicrobial agents. These agents may be present at levels of fromabout 0.01% to about 1.5%, by weight of the dentifrice composition. Theoral compositions of the present invention are in the form oftoothpastes, dentifrices, topical oral gels, mouthrinses, dentureproducts, mouthsprays, lozenges, oral tablets, or chewing gums. Thedentifrice compositions may be a paste, gel, or any configuration orcombination thereof.

EXAMPLES

The following examples further describe and demonstrate the preferredembodiments within the scope of the present invention. The examples aregiven solely for the purpose of illustration and are not to be construedas limitations of the present invention since many variations thereofare possible without departing from the spirit and scope of theinvention. Ingredients are identified by chemical name, or otherwisedefined below.

Powder Stain Prevention Model (PSPM)

The Powder Stain Prevention Model (PSPM) is a screening technique wherehydroxyapatite powder (HAP) is used as a substrate for stainaccumulation. The general purpose of this technique is to illustrate andquantify the stain prevention ability or staining potential of chemicalagents used in oral care. Hydroxyapatite powder provides a large surfacearea to which tea chromogens adsorb. Pretreatment of HAP with oral careactives, either in rinse or dentifrice form, results in different levelsof stain accumulation depending upon the ability of the actives to blockor enhance the binding of these chromogens onto HAP surface. Themagnitude of stain can then be quantified by image analysis. Stepsinvolved in PSPM are described below.

1. HAP Pretreatment

Measure 200 mg-210 mg of HAP powder (BioGel® HTP-Gel Catalog #130-0421,Bio-Rad Laboratories (Hercules, Calif.) into 50 ml centrifuge tubes. Add20 ml of treatment to each tube. For simple polymer the treatment is a 2wt % of polymer or control at 100% active basis is used. For dentrificeformulations, weigh 8 g of each of the toothpaste into labeled 50 ground bottom centrifuge tubes. Add 24 g of deionized water into thetubes (so that the slurry ratio is 1:3). Vortex for 1 min to mix well toprepare the slurry with no chunks of toothpaste. Centrifuge the slurryfor 15 min at 15,000 rpm using the centrifuge and use 20 mL ofsupernantent as the treatment. Tube is vortexed for 30 seconds to fullysuspend HAP in treatment followed by centrifugation at 15,000 rpm for 15mins. After centrifugation, supernatant is decanted and pelletredistributed by adding 25 ml of water, vortexing, centrifuging at15,000 rpm for 15 mins, and decanting—making sure pellet breaks upduring vortexing. The wash cycle is repeated two more times.

2. HAP Staining

After final water wash, 20 ml of filtered tea (1 Lipton tea bag per 100ml of hot water seeped for 5 minutes, filtered and used at 50° C.) isadded to each pellet and vortexed for 30 seconds to fully suspend HAP intea. Powder suspension is centrifuged at 15,000 rpm for 15 mins anddecanted. About 25 ml of water is added to the tube, vortexed and thencentrifuging at 15,000 rpm for 15 mins. The liquid is decanted and washcycle is repeated 2 more times.

3. HAP Prep for Color Analysis

Vortex pellet in approximately 10 ml of water until fully suspendedfollowed by filtering under vacuum onto a Millipore filter disk(Membrane Filters 4.5 tm, 47 mm Catalog #HAWPO4700, MilliporeCorporation, Bedford, Mass.). Prepare a control disk using. −200 mg ofuntreated, unstained HAP. Filter disks are then dried overnight in flatposition and then laminated.

4. Color Analysis of Stained HAP

Whitelight system: HAP disk (untreated HAP control and HAP treatments)is placed in a stabilized sample holder. The color is measured using adigital camera having a lens equipped with a polarizer filter (Cameramodel no. CANON EOS 70D from Canon Inc., Melville, N.Y. with NIKON 55 mmmicro-NIKKOR lens with adapter). The light system is provided by Dedolights (model number DLH2) equipped with 150 watt, 24V bulbs modelnumber (Xenophot model number HL X64640), positioned about 30 cm apart(measured from the center of the external circular surface of one of theglass lens through which the light exits to the other) and aimed at a 45degree angle such that the light paths meet on the HAP disk. Imageanalysis is performed using Whitelight with Ultragrab, Optimas and GiantImaging software.

5. Controls

Usual controls for a single polymer PSPM are water as a treatmentfollowed by exposure to tea, and water without exposure to tea.Additionally, pyrophosphate and polyphosphate are run as internalcontrols.

6. Results

Calculate changes in L* (brightness), a* (red(+)/green(−)), b*(yellow(−)/blue(+)), and in E (total color) as follows:ΔL=L* _(untreated HAP) −L* _(treated HAP)Δa=a* _(untreated HAP) −a* _(treated HAP)Δb=b* _(untreated HAP) −b* _(treated HAP)ΔE=√{square root over ((ΔL)²+(Δa)²+(Δb)²)}

Report results as average ΔL, Δ a, Δb, and/or ΔE and percent preventionof stain (AL & AE) versus the negative control.

Powder Stain Removal Model (PSRM)

The Powder Stain Removal Model (PSRM) is a screening technique wherehydroxyapatite powder (HAP) is used as a substrate for stainaccumulation. The purpose of this technique is to illustrate andquantify the stain removal properties of chemical agents used in oralcare. Hydroxyapatite powder provides a large surface area to which teachromogens adsorb. Treatment of stained HAP with oral care actives,either in rinse or dentifrice form, results in different levels of stainremoval depending upon the ability of the actives to disrupt the bindingof these chromogens onto HAP surface. The magnitude of stain removal canthen be quantified by image analysis. A trial of this model can becompleted in three days. Steps involved in PSRM are described below.

1. HAP Staining

Prepare large batch of tea stain HAP by stirring 10 g of HAP powder in200 ml of filtered tea for 5 minutes. Divide into centrifuge tubes andcentrifuge at 15,000 rpm for 15 mins. Wash pellet by adding in 25 ml ofwater, vortexing, centrifuging at 15,000 rpm for 15 mins, and pipet outliquid. Make sure pellet breaks up during vortexing. Repeat wash.

Place centrifuge tubes in convection oven (55-65° C.) overnight to drystained HAP. Once dried, pool stained HAP together and grind to a finepowder with pestle and mortar.

2. HAP Treatment

Measure 200 mg-210 mg of HAP powder (BioGel® HTP-Gel Catalog #130-0421,Bio-Rad Laboratories (Hercules, Calif.) into 50 ml centrifuge tubes. Add20 ml of treatment to each tube. For simple polymer the treatment is a 2wt % of polymer or control at 100% active basis is used. For dentrificeformulations, weigh 8 g of each of the toothpaste into labeled 50 ground bottom centrifuge tubes. Add 24 g of deionized water into thetubes (so that the slurry ratio is 1:3). Vortex for 1 min to mix well toprepare the slurry with no chunks of toothpaste. Centrifuge the slurryfor 15 min at 15,000 rpm using the centrifuge and use 20 mL ofsupernantent as the treatment. Tube is vortexed for 1 minute to fullysuspend HAP in treatment followed by centrifugation at 15,000 rpm for 15mins. After centrifugation, supernatant is decanted and pelletredistributed by adding 25 ml of water, vortexing, centrifuging at15,000 rpm for 15 mins, and decanting—making sure pellet breaks upduring vortexing. The wash cycle is repeated one more time.

3. HAP Prep for Color Analysis

Vortex pellet in approximately 10 ml of water until fully suspendedfollowed by filtering under vacuum onto a Millipore filter disk(Membrane Filters 4.5 tm, 47 mm Catalog #HAWPO4700, MilliporeCorporation, Bedford, Mass.). Prepare a control disk using ≈200 mg ofuntreated, stained HAP. Filter disks are then dried overnight in flatposition and then laminated.

4. Color Analysis of Stained HAP

Whitelight system: HAP disk (untreated HAP control and HAP treatments)is placed in a stabilized sample holder. The color is measured using adigital camera camera having a lens equipped with a polarizer filter(Camera model no. CANON EOS 70D from Canon Inc., Melville, N.Y. withNIKON 55 mm micro-NIKKOR lens with adapter). The light system isprovided by Dedo lights (model number DLH2) equipped with 150 watt, 24Vbulbs model number (Xenophot model number HL X64640), positioned about30 cm apart (measured from the center of the external circular surfaceof one of the glass lens through which the light exits to the other) andaimed at a 45 degree angle such that the light paths meet on the HAPdisk. Image analysis is performed using Whitelight with Ultragrab,Optimas and Giant Imaging software.

5. Controls

Usual controls for a single polymer PSRM are water as a treatmentfollowed by exposure to tea, and water without exposure to tea.Additionally, pyrophosphate and polyphosphate are run as internalcontrols.

6. Results

Calculate changes in L* (brightness), a* (red(+)/green(−)), b*(yellow(−)/blue(+)), and in E (total color) as follows:ΔL=L* _(untreated HAP) −L* _(treated HAP)Δa=a* _(untreated HAP) −a* _(treated HAP)Δb=b* _(untreated HAP) −b* _(treated HAP)ΔE=√{square root over ((ΔL)²+(Δa)²+(Δb)²)}

Report results as average ΔL, Δ a, Δb, and/or ΔE and percent preventionof stain (AL & AE) versus the negative control.

In-Vitro Pellicle Tea Stain Model (iPTSM)

Tooth staining is a common undesirable side effect of the use ofstannous fluoride compositions. Improved stannous fluoride dentifricesdescribed herein provide reduced dental stain formation resulting frommore efficient stannous delivery from stannous bound to the polymericmineral surface active agent. The staining of the tooth surfacetypically caused by stannous is measured in the clinical situation byusing a stain index such as the Lobene or Meckel indices described inthe literature. For rapid screening of technologies to help mitigatestannous induced staining, an in vitro lab method is used that providesquantitative estimates of stain prevention potential of stannousfluoride formulations. This method, called iPTSM (in-vitro pelliclestain model), has been shown to correlates well with clinicalobservations.

The in vitro pellicle tea stain model (iPTSM) is a technique where an invitro plaque biomass is grown on glass rods from pooled human stimulatedsaliva over the course of three days. The plaque biomass is treated withagents to determine potential dental staining levels of the variousagents. The purpose of this technique is to provide a simple and quickmethod for determining if compounds have a direct effect on the amountof dental plaque stain. This method utilizes plaque grown on polishedglass rods from pooled human saliva with treatments of 5 minutesduration, followed by a 10 minute tea treatment. A trial of this invitro model can be completed in five days during which up to 12treatments, including controls can be evaluated.

1. Roughening Glass Rods

Polish new glass rods (5 mm×90 mm) approximately 25 mm from theuntapered end on a lathe with silicon carbide paper of 240, 320, 400,and 600 grit used sequentially. After the initial polishing, polish therods with 600 grit paper only before each test.

2. Saliva Collection & Preparation

Collect saliva daily from a panel of 5-10 people by paraffin stimulationand refrigerate at 4° C. till needed. Pool saliva carefully (so not topour in wax/mucus) and mix thoroughly.

3. Day 1: Clean glass rods by sonicating with dilute HCl acid, rinse,dry, and polish with 600 grit silicon carbide paper. Rinse rods againwith DI water and dry. Insert rods into holders, adjust depth with thedepth gauge on the treatment rack, and secure rods in place with rubberO-rings.

In the early afternoon, pipette 7 ml of saliva, to which 0.1 wt %sucrose has been added, into 16×75 mm test tubes in a dipping rack.Sucrose is added to saliva on the first day only. Place the rod holdersin a modified 37° C. incubator designed to dip roughened glass rods intotest tubes to a depth of 1.5 cm at 1 rpm. Dip rods overnight. The designof the incubator is fully shown in Attachment 1. Prepare plaque growthmedia described above and autoclave for Day 2 (saliva is added on Day 2before use).

4. Day 2: In the morning, add saliva to plaque growth media and mixthoroughly. Pipette 7 ml of plaque growth media into new 16/75 mm testtubes in new dipping rack. Remove old rack of used tubes, place newdipping rack into incubator, and dip rods for six hours MINIMUM beforereplacing rods into fresh saliva for overnight dipping.5. Day 3: On the morning of the third day, pipette 10 ml of DI waterinto 17×100 mm test tubes in the second and third rows of the treatmentrack. This applies to dentifrice treatments only. Rinse solutions may ormay not have water rinse tubes in the treatment rack. Pipette freshpooled saliva into a dipping rack and set aside. Begin tea preparationby adding 550 ml to a glass beaker and heating it in the microwave for10 minutes. At the end of ten minutes, carefully remove beaker frommicrowave and drop in a magnetic stir bar to dissipate the possiblepresence of a super-heated water core. Place 5 Lipton tea bags and aCelsius thermometer into the water and stir on a hot plate. Thissolution needs to be monitored to insure that it will be no hotter than50° C. when tea treatment begins. While tea treatment is heated andmixed, prepare dentifrice slurries (1 part dentifrice to 3 parts water,also called a 1 in 4 dilution) using a handheld homogenizer for 30seconds. Centrifuge slurries for 15 minutes at 10000 rpm. Rinse oractive solutions are treated neat. Pipette 7 ml of 50° C. tea solutioninto a separate dipping rack. Add 5 ml of supernatant/rinse to 16×75 mmglass test tubes in the first row of the treatment rack. Turn offincubator dipping mechanics and remove old saliva dipping rack. Removeall rod holders from the incubator and place submerged rods into oldsaliva dipping rack to prevent drying over. Using one rod holder at atime, treats by soaking for 5 minutes in the treatment rack. Ifapplicable, wash rods with 2×10 sec dipping in the test tubes containingthe DI water in the treatment rack. Place rod holders into prepared teasolution dipping rack and soak for 10 min. Repeat this process with allfour rod holders, returning holders to dipping rack to prevent dryingout. Place fresh saliva dipping rack into incubator. Return rods to theincubator after treatment/tea soak and dip in fresh saliva for atMINIMUM of 1 hour. This treatment cycle is repeated two more times withfresh treatment/tea/saliva solutions for a total of 3 treatments in aday. After the last treatment, return rods to the incubator and dipovernight in fresh saliva.6. Day 4: On the morning of the fourth day, turn off incubator dippingmechanics and remove rods from the saliva. Allow rods to dry are thenweigh to the nearest 0.1 mg. Record weight and calculate mean dry plaquebiomass weights and standard deviations. Place rods into clean sterilecap-able test tubes containing 3 ml of 0.5M KOH, cap tightly and digestovernight at 37° C.7. Day 5: On the fifth day, remove rods from the incubator and allowcooling. Vortex glass rods to insure all deposits are homogenized.Remove rods from test tubes, filter the solution through 0.45 μmcellulose acetate syringe filters and an read absorbance values for eachrod at 380 nm in spectrophotometer. Record results and use absorbancevalues to calculate mean absorbance value per treatment, standarddeviations per treatment, mean absorbance per mg plaque, Standarddeviations of mean absorbance per mg plaque, and % increase inabsorbance per mg plaque vs. control according to the followingequation,% Stain Potential=((Test Product Abs/biomass−Non stannous controlAbs/Biomass)/(High Stannous control Abs/Biomass−Non stannous controlAbs/Biomass))*100

Example 1—Synthesis of Vinyl Phosphono-monoPhosphate (VPP) or[vinylphosphonic phosphoric anhydride]

A magnetically stirred dry 500 ml 1 neck round bottom flask was chargedwith vinyl phosphonic acid (VPA, 25.0 g, 231.5 mmole) and 300 ml DMFunder nitrogen. The resulting mixture was stirred for 10 minutes at roomtemperature yielding a homogenous solution. The tributylamine (64.3 g,82.7 ml, 1.5 equivalents) was added and stirred 30 min at roomtemperature yielding a turbid solution that separated into a small upperlayer and bulk lower layer on standing.

A second magnetically stirred dry 1000 ml 1 neck round bottom flaskfitted with an addition funnel and under nitrogen was charged1,1′-Carbonyldiimidazole (CDI), (45.1 g, 1.2 equivalents) followed by300 ml DMF. The resulting mixture was stirred 10 min at room temperatureyielding a homogenous solution. Next, the tributylamine/vinyl phosphonicacid solution was added to the CDI solution via the addition funnel overapproximately two hours and the resultant mixture was stirred at roomtemperature overnight yielding a light yellow homogenous solution.

A third magnetically stirred 2000 mL 3 neck round bottom flask fittedwith an addition funnel was charged with H₃PO₄ (56.7 g, 2.5 equivalents)followed by 400 ml DMF under nitrogen. Resulting mixture was stirred for15 min at room temperature yielding a homogenous solution. To thismixture was added tributylamine (128.7 g, 165.4 ml, 3.0 equivalents) andthe resultant was stirred 30 min yielding a turbid solution. To thisturbid solution was added the solution from the second flask overapproximately 2 hours via the addition funnel. The resultant was stirredovernight at room temperature to yield a light yellow turbid solution.This solution was stripped of solvent under vacuum (13 Torr) to a finaltemperature of approximately 70° C. to yield 226 g light yellow syrup.

The resultant was dissolved in 450 ml of water and the pH was adjustedto 10.5 with 50% NaOH (˜110 g) yielding 2 phase system. The loweraqueous phase was separated from the upper organic phase. The aqueousphase was stripped of water to a final temperature of approximately 70°C. and vacuum of 13 Torr to yield 212 g of a yellow oil. This oil washeated to approximately 60° C. and 300 ml MeOH was added over 5 min toyield a white precipitate. The MeOH was decanted from the precipitatewhich was dried to 150.6 g in an oven. P-NMR on the precipitate showedthe anticipated phosphono-monophosphate product with 1.22 molarequivalents of orthophosphate, 0.29 equivalents of pyro-phosphate and0.05 molar equivalents of starting vinyl phosphonic acid. H-NMR alsoshowed product, starting material, residual solvents and approximately0.4 molar equivalents imidazole.

For further purification, the precipitant was dissolved in 300 ml water.Under rapid stirring, 400 ml of MeOH was added over 30 minutes. Theresulting white precipitant was collected by filtration, rinsed with 100ml MeOH and dried overnight to yield 102.4 g. P-NMR's on thisprecipitant showed it to be primarily orthophosphate with 0.06 moleequivalents of phosphono-monophosphate product and 0.29 mole equivalentsof pyrophosphate.

The water MeOH filtrate was stripped of solvent to a final temperatureof approximately 70° C. and pressure of 13 Torr to yield 81.94 g whitesolid. This solid was shown to be primarily vinylphosphono-monophosphate with 0.077 molar equivalents of vinylphosphonate and 0.091 molar equivalents of orthophosphate. Residualimidazole was extracted from this white solid by rapid stirring thesolid in 300 ml MeOH at 40° C. 1 hr, filtering off the insoluble solidswhile the solution was hot, then rinsing the resulting solids twice with50 ml of room temperature MeOH and drying the resultant solid under highvacuum overnight at room temperature to yield 54.8 g of white powder.

P-NMR on this final sample showed vinyl phosphono-monophosphate with0.05 molar equivalents of orthophosphate, 0.04 equivalents ofpyrophosphate and 0.02 equivalents of vinyl phosphonate. The H-NMR wasconsistent with vinyl phosphono-monophosphate product with 0.02 molarequivalents of imidazole and 0.09 equivalents of methanol. Using aninternal standard, the total active was calculated to be 80.8%, whichrepresents a yield of 82%.

Example 2—Synthesis of Methyl-Vinyl Phosphono-monoPhosphate (MVPP) or[methylvinylphosphonic phosphoric anhydride]

The procedure of Example 1 was followed with the substitution ofmethy-vinyl phosphonic acid for vinyl phosphonic at 1/14 molar scale ofExample 1. Final purity was 71.9% and yield was 31.2%.

Example 3—Synthesis of (Methylenyl Phosphono-monoPhosphate)-Methacrylate[or ((methacryloxyloxy)methyl)phosphonic phosphoric anhydride]

A magnetically stirred dry 50 ml 1 neck round bottom flask was chargedwith (Methylenyl Phosphonic Acid)-Methacrylate (0.5 g, 2.77 mmole) and10 ml DMF under nitrogen. The resulting mixture was stirred for 10minutes at room temperature yielding a homogenous solution. Thetributylamine (0.77 g, 1.0 ml, 1.5 equivalents) was added and stirred 30min at room temperature yielding a homogenous solution.

A second magnetically stirred dry 10 ml 1 neck round bottom flask fittedunder nitrogen was charged 1,1′-Carbonyldiimidazole (CDI), (0.54 g, 1.2equivalents) followed by 10 ml DMF. The resulting mixture was stirred 10min at room temperature yielding a homogenous solution. Next, thetributylamine/(Methylene Phosphonic Acid)-Methacrylate solution wasadded to the CDI solution over 1 minute and the resultant mixture wasstirred at room temperature 4 hours yielding a light yellow homogenoussolution.

A third magnetically stirred 50 mL 1 neck round bottom flask was chargedwith H₃PO₄ (0.68 g, 2.5 equivalents) followed by 15 ml DMF undernitrogen. Resulting mixture was stirred for 15 min at room temperatureyielding a homogenous solution. To this mixture was added tributylamine(1.54 g, 2.0 ml, 3.0 equiv.) and the resultant was stirred 30 minyielding a turbid solution. To this turbid solution was added thesolution from the second flask over 1 minute. The resultant was stirredovernight at room temperature to yield a light yellow turbid solution.This solution was stripped of solvent under vacuum (13 Torr) to a finaltemperature of approximately 65° C. to yield 24.5 g light yellow syrup.

The resultant was dissolved in 100 ml of water and the pH was adjustedto 8 with 1N NaOH (˜14 g) yielding a milky white system, which wassubsequently concentrated at 65° C. and 13 Torr to 24.5 g of lightyellow syrup. This syrup was added to 50 ml MeOH was added over 5 min toyield a white precipitate. The MeOH was decanted to remove theprecipitate, then the MeOH was stripped under vacuum to yield 7.4 g ofgelatinous solids. P-NMR on the gelatinous solids showed the anticipatedphosphono-monophosphate product with 1 equivalent product, 0.55 molarequivalents of orthophosphate, 0.40 equivalents of the anhydride ofstarting phosphonate.

The bulk of gelatinous solids was stirred in 50 ml EtOH 1 hr at RTyielding an insoluble ppt. The ppt was filtered, rinsed twice with 10 mLof fresh EtOH and hood dried O/N to 238 mg solids. The P-NMR of thesolids showed product peaks doublets (1.1/1.0 ppm & −8.4/−8.5 ppm),phosphate (2.04 ppm), product anhydride (2.9 ppm) in a ratio of100:70:10 as well as other minor unknowns. The H-NMR shows the driedsolids to be consistent with product containing ˜12 mole % imidazole,residual EtOH and other minor unknowns.

Example 4—Synthesis of (Ethyl Phosphono-monoPhosphate) (Butyl)Acrylamide or [(2-(N-butylacrylamido)ethyl)phosphonic phosphoricanhydride]

A magnetically stirred dry 25 ml 2 neck round bottom flask was chargedwith n-butylamine (6.3 mL, 63 mmole) and heated under dry nitrogen to78° C. Diethyl vinyl phosphonate (1.0 ml, 6.3 mmole) was added andstirred overnight. Resulting mixture was rotary evaporated at around 45°C. and 20 mmbar to recover 1.38 g of material at high purity diethylethyl phosphonate butyl amine by P-NMR (92% recovery).

A magnetically stirred dry 25 ml 2 neck round bottom flask was chargedwith diethyl ethyl phosphonate butyl amine (1.1 g, 4.6 mmole), 2 mL ofdichloromethane and 6 mL of 1N NaOH. Resultant was stirred and cooled inan ice bath. A mixture of 2 mL of dichloromethane and 0.368 g ofacryloyl chloride was added dropwise to this flask over 30 minutes.Resultant was diluted with 10 mL of dichloromethane extracted in aseparatory funnel 2×25 mL 1N HCl, 1×25 mL saturated NaCl with 10 mLrinses with dichloromethane of the aqueous phases. Resulting combinedorganic phases were dried over anhydrous sodium sulfate and filtered.Solvent was removed by rotary evaporation at approximately 35° C. toyield 0.84 g (72%) of product.

The ethyl ester groups on this product were removed by dissolving theentire lot in 4 mL of dichloromethane in a magnetically stirred 100 mL 2neck flask under dry nitrogen in an iced bath then adding a mixture of 1mL dichloromethane and 2 mL of trimethyl bromo silane over 20 minutes.An additional 1 mL of dichloromethane and then a mixture of 1 mL ofdichloromethane and 1 mL of trimethyl bromo silane were then added.After 2 hours, 30 mL of MeOH was added and allowed to stir for 10minutes followed by 0.21 mg of butylated hydroxy toluene in 1 mLdichloromethane. Volatiles were removed by rotary evaporate at around40° C. Resultant was purified by dissolving in 50 mL of dichloromethaneand extracting with a mixture of 25 mL of 0.1 N NaOH and 25 mL of 1 NNaOH. Aqueous phase was extracted a second time with 25 mL ofdichloromethane than acidified with to pH 1 with 1N HCl then rotaryevaporated to near dryness. Resulting residue was diluted with 50 mL ofEtOH and rotary evaporated to near dryness 3 times to remove the water.Resultant residue was then diluted with 10 mL of pentane and evaporatedto near dryness 2 times to remove residual EtOH. Final recovery nearquantitative.

Addition of the phoshono-phosphate group was performed as in Example 3.The purification step was slightly modified. An diethyl ether (1 volumeequivalent) extraction was performed on the crude reaction mixture thenthe solution was vacuum stripped at 30-35° C. Residues was dissolved in25 mL of water and the pH adjusted to 7 with 1N NaOH followed by vacuumstripping of water at 40-45° C. to leave a liquid residue. Next, 100 mLof methanol was added to the residue resulting in a precipitant that wascollected and dried under vacuum to yield approximately 9.1 grams at 80%active by P-NMR.

Example 5—Synthesis of (4-VinylBenzyl) Phosphono-monoPhosphate or[(4-vinylbenzvl)phosphonic phosphoric anhydride]

A magnetically stirred dry 50 ml 1 neck round bottom flask was chargedwith (4-VinylBenzyl) Phosphonic Acid (4.0 g, 20.2 mmole) and 20 ml DMFunder nitrogen. The resulting mixture was stirred for 10 minutes at roomtemperature yielding a homogenous solution. The tributylamine (5.6 g,7.2 ml, 1.5 equivalents) was added and stirred 30 min at roomtemperature yielding a homogenous solution. A second magneticallystirred dry 10 ml 1 neck round bottom flask fitted under nitrogen wascharged 1,1′-Carbonyldiimidazole (CDI), (4.9 g, 1.2 equivalents)followed by 25 ml DMF. The resulting mixture was stirred 10 min at roomtemperature yielding a homogeneous solution. Next, thetributylamine/(4-VinylBenzyl) Phosphonic Acid solution was added to theCDI solution over 1 minute and the resultant mixture was stirred at roomtemperature 4 hours yielding a light yellow homogeneous solution.

A third magnetically stirred 100 mL 1 neck round bottom flask wascharged with H₃PO₄ (5.94 g, 3.0 equiv) followed by 25 ml DMF undernitrogen. Resulting mixture was stirred for 15 min at room temperatureyielding a homogeneous solution. To this mixture was added tributylamine(13.1 g, 16.8 ml, 3.5 equivalents) and the resultant was stirred 30 minyielding a turbid solution. To this turbid solution was added thesolution from the second flask over 1 minute. The resultant was stirredovernight at room temperature to yield a light yellow solution. Thissolution was stripped of solvent under vacuum (13 Torr) to a finaltemperature of approximately 65° C. to yield 49.8 g light yellow syrup.The resultant was added to 30 ml of water and the pH was adjusted to 8.5with 1N NaOH (˜127 g) yielding a milky white system, which wassubsequently concentrated at 65° C. and 13 Torr to 58.2 g of lightyellow syrup. This syrup was added to 40 ml MeOH was added over 20 minto yield a white precipitate. P-NMR on the paste showed it to beapproximately 95% phosphate. The MeOH was decanted to remove theprecipitate, then the MeOH was stripped to yield 7.23 g of white paste.The P NMR on the white paste showed the anticipatedphosphono-monophosphate product with 1 equivalent product, 0.16 molarequivalents of orthophosphate, 0.05 equivalents of pyrophosphate, 0.25equivalents of the anhydride of starting phosphonate and 0.065equivalents of starting phosphonate.

The bulk of the white paste was stirred in 75 ml MeOH 1 hr at roomtemperature. A portion of the paste dissolved, however a portionremained insoluble. The insoluble portion was filtered and rinsed twicewith 10 mL of fresh MeOH. The resulting solid was dried under highvacuum O/N to yield 1.97 g solids. The P-NMR of the solids showedproduct peaks doublets (1.1/1.0 ppm &−8.4/−8.5 ppm), phosphate (2.04ppm), product anhydride (2.9 ppm) in a ratio of 100:70:10 as well asother minor unknowns. The H-NMR shows the dried solids to be consistentwith product containing ˜12 mole % imidazole, residual EtOH and otherminor unknowns. The yield of the final solids was 23.7% of theoretical.

Example 6—Synthesis of (Bis(Methylene PhosphonateAnhydride)Aminopropyl)-Methacrylate Polymer or[4-(3-(methacryloyloxy)propyl)-1,4,2,6-oxazadiphosphinane-2,6-bis(olate)2,6-dioxide Polymer]

A magnetically stirred dry 250 ml 3 neck round bottom flask was chargedwith (Bis(Methylene Phosphonic Acid)aminopropyl)-Methacrylate (3.0 g,9.06 mmole) and 100 ml DMF under nitrogen. The resulting mixture wasstirred for 10 minutes at room temperature yielding a homogeneoussolution. The tributylamine (5.03 g, 6.5 ml, 3.0 equivalents) was addedand stirred 30 min at room temperature yielding a homogeneous solution.

A second magnetically stirred dry 100 ml 1 neck round bottom flaskfitted with an addition funnel and under nitrogen was charged1,1′-Carbonyldiimidazole (CDI), (2.2 g, 1.5 equivalents) followed by 40mL DMF. The resulting mixture was stirred 10 min at room temperatureyielding a homogenous solution. The CDI solution was added via additionfunnel over approximately one hour to the first flask and the resultantmixture was stirred at room temperature overnight followed by standingfor 1 week to yield a white precipitate. The precipitant was collectedby filtration, slurried in 100 mL water and the pH adjusted to ≈9 with1N NaOH yielding a turbid solution. This solution was evaporatedovernight under flowing air to 2.4 g. The H & P-NMR's showed theprecipitant to be polymer with some monomer. The P-NMR showed polymerictarget anhydride (at 12-13 ppm) and starting di-acid (at 6-7 ppm) aswell as monomer peaks (at 11.8-12 ppm) in a ratio of 36:53:11. The bulkof the precipitant was sonicated in 100 mL water 1 hr yielding a turbidsolution which was filtered using a 250 mL Stericup Durapore with 0.22μm PVDF filter disk yielding a clear solution. This was brought up to250 ml and purified by dialysis in a Thermo Scientific Slide-A-Lyzerdialysis flask (2K MWCO, 250 ml) against 5 gallons RO water (pH adjustedto 8.5 w 1N NaOH) for 7 days yielding 1.29 g white solid (17-DF-5835-5)after freeze drying. The P-NMR showed a broad anhydride peak at 12-13ppm & a di-acid peak at 6.4-7.4 ppm in a 39.2:60.8 molar ratio. Activitywas calculated to be 87.8% polymer & 12.2% water/inactives.

Example 7—Synthesis of (Ethyl Phosphono-monoPhosphate)-Methacrylate or[(2-(methacryloyloxy)ethyl)phosphonic phosphoric anhydride]

A magnetically stirred dry 100 ml 1 neck round bottom flask was chargedwith (Ethyl Phosphonic Acid)-Methacrylate (3 g, 15.5 mmole) and 30 mlDMF under nitrogen. The resulting mixture was stirred for 10 minutes atroom temperature yielding a homogenous solution. The tributylamine (4.3g, 5.5 ml, 1.5 equivalents) was added and stirred 30 min at roomtemperature yielding a homogeneous solution.

A second magnetically stirred dry 25 ml 1 neck round bottom flask fittedunder nitrogen was charged 1,1′-Carbonyldiimidazole (CDI), (3.76 g, 1.5equivalents) followed by 20 ml DMF. The resulting mixture was stirred 10min at room temperature yielding a homogeneous solution. Next, thetributylamine/(Ethyl Phosphonic Acid)-Methacrylate solution was added tothe CDI solution and the resultant mixture was stirred at roomtemperature 4 hours yielding a light yellow homogeneous solution.

A third magnetically stirred 500 mL 1 neck round bottom flask wascharged with H₃PO₄ (4.55 g, 3.0 equivalents) followed by 25 ml DMF undernitrogen. Resulting mixture was stirred for 15 min at room temperatureyielding a homogeneous solution. To this mixture was added tributylamine(12 g, 15.4 ml, 4.2 equiv.) and the resultant was stirred 30 minyielding a turbid solution. To this turbid solution was added thesolution from the second flask over 1 minute. At about 1 hour ofstirring, a white precipitant began to form. The resultant was stirredovernight at room temperature with additional precipitant forming. TheP-NMR showed product peaks doublets (7.2/7.3 ppm &−8.75/−8.84 ppm),phosphate (2.14 ppm), product anhydride (8.9 ppm) & pyrophosphate (−9.26ppm) in a ratio of 100:427:12:15.

To the crude Rx solution (≈90.7 g) was added with stirring 200 mL ethylether over 30 min yielding a white ppt which was collected byfiltration, rinsed with additional ether and dried overnight undervacuum (<1 Torr) at room temperature to yield 7.85 g white precipitant.To the resultant filtrate was added an additional 200 mL ethyl etherwith stirring over 30 min yielding a two layer system with a freeflowing top layer and lower viscous oil layer. The top layer wasdecanted and the lower oil layer dried overnight under vacuum (<1 Torr)at room temperature to 2.33 g waxy solid. To the decanted layer wasadded an additional 400 ml ether over 30 min with stirring yielding aturbid solution. The turbid solution was placed in a freezer (−15° C.)overnight yielding a clear free flowing top layer and a viscous oillower layer. The top layer was decanted and the lower oil layer driedovernight under vacuum (<1 Torr) at room temperature to 1 hr to 1.19 gwaxy solid.

The white precipitant was shown by H-NMR to be a mixture ofproduct:imidazole:tributyl amine in a molar ratio of 100:1150:220, whilethe P-NMR showed a mixture of product:phosphate:pyro in a molar ratio of100:625:35.

The first waxy solid was shown by H-NMR to be a mixture ofproduct:imidazole:tributyl amine in a molar ratio of 100:230:170. TheP-NMR showed a mixture of product:phosphate in a molar ratio of 100:89.

The second waxy solid was shown by H-NMR to be a mixture ofproduct:imidazole:tributyl amine in a molar ratio of 100:100:150. TheP-NMR showed a mixture of product:phosphate in a molar ratio of 100:79.

Waxy solids were combined and dissolved in 50 mL deionized water. The pHof the resultant solution was adjusted from 2.9 to 8.6 with 19.3 g 1NNaOH yielding a turbid solution. This solution was extracted 1× with 50mL ethyl ether. The resultant aqueous layer had a pH=7.5 was trimmed to8.0 with additional 1N NaOH. Residual ether was removed form the aqueouslayer on roto-vap at room and 20 Torr. The water was removed from theaqueous layer via freeze-drying yielding 2.61 g tan solid.

The H & P-NMR's showed a mixture of product:imidazole:NBut3 in a molarratio of 100:160:50. The P-NMR shows a mixture of product:phosphate in amolar ratio of 100:101.

Tan solid was stirred in 50 mL MeOH for 30 min yielding an insolublesolid. Solid was collected by filtration, rinsed 2×10 ml fresh MeOH anddried overnight at room temperature at <1 Torr to yield 1.79 g creamcolored solid. The H-NMR's was consistent with product containing ˜1mole % imidazole. The LCMS demonstrated a mass consistent with the M+Hprotonated form at 273. The H-NMR of methanol extract showed it to beprimarily imidazole containing ˜3 mole % product. Activity wascalculated by combined H-NMR and P-NMR and found to be 74.4%.

Example 8—Synthesis of (Propyl Phosphono-monoPhosphate)-Methacrylate or[(3-(methacryloyloxy)propyl)phosphonic phosphoric anhydride]

The procedure of Example 7 was followed substituting 5.5 g (26.4 mmol)(Propyl Phosphonic Acid)-Methacrylate for (Ethyl PhosphonicAcid)-Methacrylate. All reagents were scaled to keep the molarequivalence the same. After final evaporation, 5.17 g of cream solid wascollected and shown to be 67.8% active.

Example 9—Synthesis of (Ethyl Phosphono-monoPhosphate)-Acrylamide or[(2-acrylamidoethyl)phosphonic phosphoric anhydride]

The procedure of example 5 was followed using (acrylamido)ethylphosphonic acid (37 mmoles) in place of vinyl benzyl phosphonate forcreation of the crude yellow solution, with increased quantities of allreagents at equivalent molar ratios to example 5.

The purification procedure of the crude solution was modified fromexample 5. DMF was partially removed at room temperature with flowingdry nitrogen to yield 46.8 g of a viscous yellow oil. This oil wasdissolved in ≈75 mL of water and the pH adjusted to 8 by addition of 1 NNaOH over 20 minutes. A small organic layer 9.4 g of tributyl amineformed and was decanted. The aqueous phase was further dried underflowing dry nitrogen to 147.5 g, then 220 mL of MeOH was added over 30minutes to yield a white precipitate. The precipitate was filtered andthe resulting filtrate dried yield 22.7 g of brown paste, which P NMRshowed to be mostly product. The brown paste was slurried in 100 mL ofEtOH under vigorous stirring for 6 hour at room temperature. A solidformed and was collected by filtration, rinsed with fresh EtOH 2×25 mLand dried at <1 Torr overnight to yield 10.94 g of tan solid. The solidcontained 69% phosphono-monophosphate product by NMR.

Example 10—Synthesis of (Methylene Phosphono-monoPhosphate)-Acrylate or[((acryloyloxy)methyl)phosphonic phosphoric anhydride]

The procedure of Example 3 is followed substituting (MethylenePhosphonic Acid)-Acrylate for (Methylene Phosphonic Acid)-Methacrylate

Example 11—Synthesis of (Ethyl Phosphono-monoPhosphate)-Vinyl Ether or[(2-(vinyloxy)ethyl)phosphonic phosphoric anhydride]

A dry, septum sealed, nitrogen flushed, magnetically stirred 250 mLthree neck round bottom flask was charged with diethyl(2-(vinyloxy)ethyl)phosphonate (3 g, 14.4 mmol) and 30 ml CH₂Cl₂ andchilled to 0-5° C. To this flask was added bromotrimethylsilane (5.7 mL,43.2 mmol, 3.0 equivalents) over 1 minute. After addition the solutionwas stirred for 2 hours at room temperature and the solution stripped ofsolvent at 30° C. and <1 Torr to yield 4.59 g yellow oil. To this wasadded 15 g of triethylamine, 30 g MeOH and 60 mg of phenothiazine(inhibitor) that had been pre-chilled over dry ice and acetone.Resultant was allowed to warm to room temperature under constantstirring, then put under vacuum at room temperature to remove solventand volatiles for 1 hour yielding 3.84 g of viscous turbid yellow oil.P-NMR and H-NMR were consistent with amine mono-triethyl amine salt. Theprocedure of Example 7 was followed to create and purify (EthylPhosphono-monoPhosphate)-Vinyl Ether resulting in 4.04 g of tan solidafter methanol extraction. The H-NMR's was consistent with productcontaining ˜5 mole % imidazole. The P-NMR was consistent with a productphosphono-monophosphate to residual phosphate ratio of 100:112. The LCMSdemonstrated a mass consistent with the M+H protonated form at 231.Activity was calculated by combined H-NMR and P-NMR and found to be 52%.

Example 12—Synthesis of (Ethyl Phosphono-monoPhosphate)-Acrylate or[(2-(acryloyloxy)ethyl)phosphonic phosphoric anhydride]

A dry magnetically stirred IL three neck round bottom flask was chargedwith dimethyl (2-hydroxyethyl)phosphonate (24.7 g, 16 mmol), triethylamine (17.8 g 176 mmol) and 400 ml CH₂Cl₂ and chilled to 0-5° C. To thisflask was added a solution of the acryloyl chloride (14.95 g 16.51mmole) in 100 ml CH₂Cl₂ over 1.5 hours while maintaining reactiontemperature of 0-5° C. After the addition was complete the reaction tempwas maintained at 0-5° C. for an additional 2 hours followed by warmingto RT and stirring overnight.

The resulting light brown turbid solution was extracted 2×200 mldeionized water, and the oil layer dried over anhydrous MgSO₄ and thenfiltered. The filtrate was stripped of solvent yielding 30.5 g brownoil. The H, C & P-NMR's were consistent with the first intermediate,(Ethyl, dimethyl phosphonate)-Acrylate. The yield was 91.4%.

The above brown oil was charged into a dry magnetically stirred 500 mLthree neck round bottom flask with 250 mL of dichloromethane. The flaskand contents were chilled to 10° C. and 67.3 g (3 equivalents) ofbromotrimethylsilane was added over 30 minutes. The flask was allowed towarm to room temperature and stirred overnight. Resultant solution wasstripped of solvent at 30° C. followed by stirring under high vacuum (<1Torr) overnight to yield 37 g of light oil. To the oil, 200 mL ofmethanol was added over 10 minutes at room temperature followed bystirring at room temperature for 3 hours. Resultant solution wasstripped of solvent at 30° C. followed by stirring under high vacuum (<1Torr) overnight to yield 26.1 g of a viscous tan oil. H NMR and P NMRwere consistent with product. The yield was 98.9%.

The procedure of example 5 was followed using (acryloyloxy)ethylphosphonic acid in place of vinyl benzyl phosphonate for creation of thecrude yellow solution. P NMR and H NMR showed 72% yield of desiredproduct.

Example 13—Synthesis of Mixed Vinyl Phosphono-Phosphates

The procedure of Example 1 was followed with the substitution ofpyrophosphoric acid for phosphoric acid at 1/12 molar scale ofExample 1. After removal of the DMF solvent to yield a yellow oil andaddition of 1N NaOH, 24.1 g of white solid was collected after spargingovernight with nitrogen. This sample was shown by PNMR to contain vinylphosphono-pyrophosphate (VPPP), vinyl phoshono-monophosphate, startingmaterial, starting material anhydride, phosphate, pyrophosphate andtriphosphate. The ratio of vinyl phosphono pyrophosphate:vinylphosphono-monophosphate was 1:1.7.

Example 14 Synthesis of Vinyl Sulfonate Methyl Ester (VSME)

A magnetically stirred dry 500 ml 3 neck round bottom flask equippedwith an addition funnel and a thermometer was charged with 250 mL ofmethanol under nitrogen and cooled to 0° C. The 2-chloroethanesulfonylchloride (Aldrich) was added to the flask over 15 minutes with noobserved exotherm. Next 25% NaOMe/MeOH (Aldrich) was added over 2 hoursat rate to maintain a temperature of approximately 0° C. During theaddition a white precipitant, (NaCl) formed. The resultant was stirredan additional hour at 0° C. and then allowed to warm to room temperatureand stirred overnight. The precipitant was removed by filtration and thefiltrate was stripped of solvent yielding 20.33 g white gel. This gelwas slurried in 200 ml CH₂Cl₂ for 1 hour. The resultant was filtered andthe filtrate stripped of solvent yielding 9.47 g tan oil.

¹H & ¹³C-NMR's showed a mixture of desired product, VSMS, and methyl2-methoxyethane-1-sulfonate in a 3:0.6 ratio, 79.8% product by weight.The H-NMR also shows and acid peak at ˜10 ppm. A test of 0.05 g tan oilin 1 ml water showed a pH of approximately 1 by litmus.

8.8 g of tan oil was dissolved in 100 ml CH₂Cl₂ and stirred over 5 gsodium bicarbonate. The resultant was filtered and the filtrate strippedof solvent yielding 8.02 g light yellow clear oil.

A test of 0.05 g of the yellow clear oil in 1 mL water showed a pH ofapproximately 6-7 by litmus. Ratio of VSME to methyl 2-methoxyethane-1-1sulfonate was the same, yielding 79.8% active.

Example 15 Synthesis of Sodium Vinyl Benzyl Sulfonate

A magnetically stirred dry 250 ml 3 neck round bottom flask equippedwith a heating mantel, addition funnel and reflux condenser was chargedwith 9.5 g of sodium sulfite (75.5 mmol) and 100 ml water. The resultantsolution was heated to 100° C. under nitrogen. Next, 4-vinylbenzylchloride (9.6 g, 62.9 mmol) in 15 ml acetone was added over 30 minutes.The resultant was refluxed 12 hours, cooled to room temperature andallowed to stand overnight with no resulting precipitant. Next, underrapid stirring, 100 ml acetone was added resulting in a lower paste-likelayer. The water/acetone supernatant was decanted. The paste was rinsedwith 25 mL of fresh acetone which was then decanted. The paste was driedovernight under vacuum, 14 torr, and room temperature to yield 8.5 gsolids. This dried layer was shown to be primarily homopolymer by¹H-NMR. The water/acetone decanted layers were evaporated toapproximately 75 ml yielding a white ppt. The ppt was collected byfiltration, rinsed 2×25 ml acetone and dried overnight under vacuum, 14torr, and room temperature to yield 2.14 g solids.

The ¹H-NMR of this second precipitant was consistent with monomerproduct at close to 100% activity.

Example 16 Co-Polymerization of Vinyl Phosphonic Acid (VPA) and SodiumVinyl Sulfonate (SVS)

VPA (2.0 g, 18.5 mmoles) and SVS (25% aqueous solution, 7.9 g, 15.2mmoles), initial molar ratio of SVS to VPA of 45 to 55, were charged ina round bottom flask. The flask was purged with nitrogen for 15 minutesand heated to 90° C. Two separate aqueous solutions containing2,2′-azobis(2-methylpropionamidine) dihydrochloride (AAPH, Aldrich, 25.8mg in 1.2 mL water, 0.3% molar basis to total monomers added) and1-Octanethiol (CTA, Aldrich 55.6 mg in 1.2 mL of water, 1.1% molar basisto total monomers added) were also prepared. These two solutions werethen added to the heated stirred flask containing the monomers every 30minutes over the course of 6 hours. After the final addition, theresulting solution was allowed to stir overnight at 90° C.

¹H-NMR & ³¹P-NMR were run on the crude reaction solutions. Typicalmonomer conversions of 95-99% were observed with a broad P polymer peakat ˜31 ppm from the phosphonate group.

The crude reaction solutions were diluted to 1 wt % polymer in water andthe pH adjusted to 6. These solutions were dialyzed with 2K molecularweight cut off dialysis membranes against reverse osmosis water for 5-7days.

The resultant solution was stripped of water under vacuum to yield whiteto cream color solids which was further dried in a vacuum oven overnightto yield 2.74 g of solid.

The phosphonate content in the polymers were determined by preparing anNMR sample with purified polymer & trimethyl phosphate (TMP) in D₂O. The¹H & ³¹P-NMR's were run from which the phosphonate content wascalculated from the H and P peaks of the internal standard (TMP)relative to the polymer peaks and water. Based on this analysis, thepolymer contained 55.7 mol % repeat units resulting from SVS and 44.3mol % repeat units resulting from VPA. The water content was calculatedto 9.6% on a weight basis. The total recovery of monomers in the postdialysis polymer was calculated to be 57% on a molar basis.

Example 17 Co-Polymerizations of Vinyl Phosphonic Acid and Sodium VinylSulfonate (SVS)

The procedure of Example 16 was repeated for different starting ratiosof VSA and VPA. The resulting polymer compositions from differentstarting ratios and total yield, including Example 16 are shown in theTable 1 below. A Wyatt Gel Permeation Chromatography (GPC) system, usinga Polymer Standards Service (PSS) MCX 1000A column and both a WyattHELEOS II light scattering detector and a Wyatt Optilab Differentialrefractive index detector, was used for calculation of polymer molecularweight using the internal Wyatt Astra 6 software.

TABLE 1 % Total % Total Total Monomer Monomer % AAPH % CTA % Sulfonate %Phosphonate Molar Mn Mw SVS Loaded VPA Loaded Loaded Loaded in Polymerin Polymer Yield (kDa) (kDa) 75.0% 25.0% 0.3% 1.0% 80% 20% 85% 5.4 7.970.0% 30.0% 0.3% 1.1% 69% 31% 66% 4.2 5.9 50.0% 50.0% 0.3% 1.0% 57% 43%73% — — 45.1% 54.9% 0.3% 1.1% 56% 44% 57% 3.4 4.5 40.0% 60.0% 0.3% 1.0%44% 56% 64% 4.2 5.3 20.0% 80.0% 0.3% 1.0% 34% 66% 58% — —

Example 18 Co-Polymerization of Vinyl Phosphonic Acid (VPA) and AcrylicAcid (AA)

The procedure in Example X was repeated using an initial charge of 19mmol of VPA in 1.5 mL of water. Acrylic acid, 28.5 mmol in 1.6 mL ofwater was added (0.3 mL) along with the 0.1 mL of AAPH and CTA every 30minutes. An additional 3 mL of water was added half way through theadditions. The final polymer collected was 2.87 g after dialysis and wasfound to be 30% phosphonate and 70% acrylate.

Example 19 Co-Polymerization of Vinyl Phosphono-monoPhosphate (VPP) andSodium Vinyl Sulfonate (SVS)

VPP (Example 1, 2.05 g active, 8.87 mmoles) and SVS (25% aqueoussolution, 3.77 g, 7.25 mmoles), initial molar ratio of SVS to VPP of 45to 55, were charged in a round bottom flask, and the headspace of theflask purged with flowing nitrogen for 15 minutes. The flask was sealedand heated to 60° C. at which time Ammonium Persulfate (APS, Aldrich,183 mg, 5% relative to total monomers) was added in 0.50 ml water. Theresultant was stirred 24 hrs at 60° C.

¹H-NMR & ³¹P-NMR were run on the crude reaction solutions. Typicalmonomer conversions of 95-99% were observed with broad P polymer peaksat ˜18 to 23 ppm from the phosphonate group and −6 to −10 from thephosphate bound to the phosphonate group.

The crude reaction solutions were diluted to 1 wt % polymer in water andthe pH adjusted to 8.5. These solutions were dialyzed with 2K molecularweight cut off dialysis membranes against reverse osmosis water for 5-7days.

Water was removed from the product by freeze drying yielding 2.22 gwhite solid.

The phosphonate content in the polymers were determined by preparing anNMR sample with purified polymer & trimethyl phosphate (TMP) in D₂O. The¹H & ³¹P-NMR's were run from which the phosphonate content wascalculated from the H and P peaks of the internal standard relative(TMP) relative to the polymer peaks and water. The P-NMR shows broadphosphono-phosponate peaks at ˜18 to 23 ppm and −6 to −10 ppm inapproximately 1:1 ratio and also a phosphonate peak at ˜26-28 ppm. Basedon the ³¹P-NMR areas at 18-23 and 26-28 ppm, thephosphono-phosphonate:phosphonate ratio is 94.9:5.1. Based on thisanalysis, the polymer contained 56 mol % repeat units resulting fromSVS, 42 mol % repeat units resulting from VPP and 2 mol % repeat unitsresulting from VPA. The water content was calculated to 23% on a weightbasis. The total recovery of monomers in the post dialysis polymer wascalculated to be 65% on a molar basis.

Example 20 Co-Polymerizations of Vinyl Phosphono-monoPhosphate (VPP) andSodium Vinyl Sulfonate (SVS)

The procedure of Example 19 was repeated for different starting ratiosof VSA and VPP. The resulting polymer compositions from differentstarting ratios and total yield, including Example 19 are shown in Table2 below.

TABLE 2 % Total % Total % Phosphono- Total Monomer Monomer % APS %Sulfonate Phosphate % Phosphonate Molar Mn Mw SVS Loaded VPP LoadedLoaded in Polymer in Polymer in Polymer Yield (kDa) (kDa) 74.9% 25.1%5.0% 81% 15% 4% 75% — — 75.0% 25.0% 5.0% 79% 20% 1% 79% — — 65.0% 35.0%5.0% 67% 30% 3% 55% — — 56.0% 44.0% 5.0% 62% 35% 3% 63% — — 55.2% 44.8%5.5% 66% 30% 3% 77% — — 50.0% 50.0% 5.2% 59% 40% 2% 65% 2.8 5.5 45.0%55.0% 5.0% 56% 42% 2% 58% — —

Example 21 Co-Polymerization of Methyl-Vinyl Phosphono-monoPhosphate(MVPP) and Sodium Vinyl Sulfonate (SVS)

The procedure of Example 19 was repeated using MVPP (Example 2) in placeof VPP and a ratio MVS to MVPP of 55 to 45, respectively, with thefollowing changes.

At 24 hours of run time, the MVPP monomer conversion via NMR was around75%, so an additional 3 mole % APS in water was added and the reactionallowed to stir for an additional 24 hours at 60° C. At this point, theMVPP monomer conversion was around 95%.

Dialysis and freeze drying were conducted as in Example 19.

Based on this NMR analysis, the polymer contained 62 mol % repeat unitsresulting from SVS, 35 mol % repeat units resulting from MVPP and 3 mol% repeat units resulting from methyl vinyl phosphonic acid. The watercontent was calculated to 10.3% on a weight basis. The total recovery ofmonomers in the post dialysis polymer was calculated to be 65% on amolar basis.

Example 22 HomoPolymerization of Vinyl Phosphono-monoPhosphate

VPP (Example 1, 16.4 mmoles) water, 6 mL, and sodium bicarbonate (0.69g, 8.2 mmoles) were charged in a 25 mL round bottom flask which was thenpurged with nitrogen for 15 minutes. Ammonium Persulfate (APS, 186.6 mg)was dissolved in 0.50 mL water and added to the mixture. The resultingsolution was allowed to stir 6 hours at 60° C. At this time, NMR showed25% polymerization monomer. An additional 186.6 mg of APS in 0.50 mL ofwater was added. The resultant was allowed to stir for a total of 24hours at 60° C. NMR showed no remaining monomer.

The crude reaction solution was diluted with 500 mL in water with aresulting pH of 8.7. This solution were dialyzed with 2K molecularweight cut off dialysis membranes against reverse osmosis water with anadjusted pH of 8.5.

The resultant solution was stripped of water under vacuum to yield whiteto cream color solids which was further dried in a vacuum oven overnightto yield 2.8 g of solid. P-NMR showed only VPP with no VPA. Theresultant was 91% polymer on a weight basis with the remaining water andimpurities. The total recovery of monomers in the post dialysis polymerwas calculated to be 58% on a molar basis.

Example 23 Co-Polymerization of Vinyl Phosphono-monoPhosphate (VPP) andSodium 2-Acrylamido-2-Methyl Propane Sulfonic Acid (AMPS)

VPP (Example 1, 6.55 mmoles) and water 2 mL were charged in a roundbottom flask, and the headspace of the flask purged with flowingnitrogen for 15 minutes. The flask was sealed and heated to 60° C. for15 minutes to yield a homogenous solution. Ammonium Persulfate (APS,149.3 mg) was dissolved in 1.2 g water. Every 30 minutes, 0.1 mL of theAPS solution and 0.206 mL of AMPS (3 g of 50% solution, 6.55 mmoles) wasadded to the reaction over a total of 6 hours. The resultant was stirred24 hrs at 60° C.

The crude reaction solution was diluted with 250 mL of water anddialyzed with 2K molecular weight cut off dialysis membranes againstreverse osmosis water for 6 days.

Water was removed from the product by freeze drying yielding 2.66 gwhite solid.

The phosphonate content in the polymers were determined by preparing anNMR sample with purified polymer & trimethyl phosphate (TMP) in D₂O. The¹H & ³¹P-NMR's were run from which the phosphonate content wascalculated from the H and P peaks of the internal standard relative(TMP) relative to the polymer peaks and water. The P-NMR shows broadphosphono-phosponate peaks at ˜18 to 23 ppm and −6 to −10 ppm inapproximately 1:1 ratio and also a phosphonate peak at ˜26-28 ppm. Basedon the ³¹P-NMR areas at 18-23 and 26-28 ppm, thephosphono-phosphonate:phosphonate ratio is 98:2. Based on this analysis,the polymer contained 64.2 mol % repeat units resulting from AMPS, 35.1mol % repeat units resulting from VPP and 0.7 mol % repeat unitsresulting from VPA. The water content was calculated to 13.3% on aweight basis.

Example 24 Co-Polymerization of Vinyl Phosphono-monoPhosphate (VPP) and3-Sulfopropyl Acrylate Potassium Salt (SPA)

The procedure of example 23 was followed with the substitution of SPA(Aldrich) for AMPS. Freeze drying of product yielded 2.04 g white solid.

Based on NMR analysis, the polymer contained 62 mol % repeat unitsresulting from SPA, 36 mol % repeat units resulting from VPP and 2 mol %repeat units resulting from VPA. The water content was calculated to15.5% on a weight basis.

Example 25 Co-Polymerization of VPP with Acrylamide

VPP (Example 1, 9.9 mmoles) and water, 3 mL, were charged in a roundbottom flask, and the headspace of the flask purged with flowingnitrogen for 15 minutes. The flask was sealed and heated to 60° C. for15 minutes to yield a homogenous solution. Ammonium Persulfate (APS,225.9 mg) was dissolved in 1.2 g water. Acrylamide (Aldrich, 9.9 mmoles)was dissolved in 1.5 g water Every 30 minutes, 0.1 mL of the APSsolution and 0.125 mL of the acrylamide solution was added to thereaction over a total of 6 hours. The resultant was stirred 24 hrs at60° C. Progress was monitored by NMR.

The crude reaction solution was diluted with 250 mL of water anddialyzed with 2K molecular weight cut off dialysis membranes againstreverse osmosis water for 5 days.

Water was removed from the product by freeze drying yielding 2.85 gwhite solid.

The phosphonate content in the polymers were determined by preparing anNMR sample with purified polymer & trimethyl phosphate (TMP) in D₂O. The¹H & ³¹P-NMR's were run from which the phosphonate content wascalculated from the H and P peaks of the internal standard relative(TMP) relative to the polymer peaks and water. The P-NMR shows broadphosphono-phosphonate peaks at ˜18 to 23 ppm and −6 to −10 ppm inapproximately 1:1 ratio. No phosphonate peak was observed at ˜26-28 ppm.Based on this analysis, the polymer contained 53 mol % repeat unitsresulting from acrylamide, 47 mol % repeat units resulting from VPP. Thewater content was calculated to 16% on a weight basis.

Example 26 Co-Polymerization of VPP with VSMS

VPP (Example 1, 7.67 mmoles), bicarbonate (Aldrich 11.5 mmol) and water,5 mL, were charged in a round bottom flask, and the headspace of theflask purged with flowing nitrogen for 15 minutes. The flask was sealedand heated to 60° C. for 15 minutes to yield a homogeneous solution.Ammonium Persulfate (APS, 174.9 mg) was dissolved in 1.2 g water. Every15 minutes, 0.1 mL of the APS solution and 0.084 mL of VSME (Vinylsulfonate methyl ester (Example 14, 79.8% Active, 7.67 mmole total) wasadded to the reaction over a total of 3 hours. The resultant was stirredan additional 3 hrs at 60° C. The crude reaction solution was dilutedwith 250 mL of water and dialyzed with 2K molecular weight cut offdialysis membranes against reverse osmosis water at a pH of 8.5 for 5days. Water was removed from the product by freeze drying yielding 2.05g white solid.

The phosphonate content in the polymers were determined by preparing anNMR sample with purified polymer & trimethyl phosphate (TMP) in D₂O. The¹H & ³¹P-NMR's were run from which the phosphonate content wascalculated from the H and P peaks of the internal standard relative(TMP) relative to the polymer peaks and water. The P-NMR shows broadphosphono-phosponate peaks at ˜18 to 23 ppm and −4 to −10 ppm inapproximately 1:1.1 ratio but no phosphonate peak at ˜26-28 ppm. Thetotal phosphorous content was 40.8%. The methyl proton from MSME wasvisible in the ¹H NMR and allowed quantification of VSME hydrolysis.Based on the total analysis, the polymer contained 39 mol % repeat unitsresulting from VSME, 20 mole % VSA, and 41 mol % repeat units resultingfrom VPP. The resultant was 73% polymer on a weight basis with theremaining water and impurities.

Example 27 Co-Polymerization of (Phosphono-monoPhosphate Ethyl) (Butyl)Acrylamide with AMPS

(Phosphono-monoPhosphate Ethyl) (Butyl) Acrylamide (Example 4, 21.6mmoles) and AMPS (23.6 mmoles) were polymerized as in Example 23. Thecrude reaction solutions were dialyzed with 1K molecular weight cut offdialysis membranes against reverse osmosis water overnight, followed by2 hours dilation agains 0.5 M NaCl and then 1 hr agains 0.05M NaCl.After freeze drying, 11.5 grams of material was collected. NMR as inother examples found the polymer to be approximately 67 mol % repeatunits resulting from AMPS, and 33% from (Phosphono-monoPhosphate Ethyl)(Butyl) Acrylamide. The solid contains around 16% water, by weight andwas 55% polymer by weight.

Example 28 Co-Polymerization of VPP with VPA

VPA (1.2 g, 11.1 mmoles) and water 6 mL were charged in a 25 mL roundbottom flask. Sodium bicarbonate (2.8 g, 33.3 mmoles) was added over 60minutes and the flask was then purged with nitrogen left to stir overnight at room temperature. VPP (Example 1, 11.1 mmoles) was added andthe solution purged with nitrogen and heated to 60° C. yielding a turbidsolution. Ammonium Persulfate (APS, 253.5 mg) was dissolved in 0.75 mLwater and added to the mixture. The resulting solution was allowed tostir 6 hours at 60° C. At this time, NMR showed 40% polymerization ofall monomers. An additional 253.3 mg of APS in 0.75 mL of water wasadded. The resultant was allowed to stir for a total of 24 hours at 60°C. NMR showed 10% remaining monomer.

The crude reaction solution was diluted with 500 mL in water with aresulting pH of 8.7. This solution were dialyzed with 2K molecularweight cut off dialysis membranes against reverse osmosis water with anadjusted pH of 8.5.

The resultant solution was stripped of water under vacuum to yield whiteto cream color solids which was further dried in a vacuum oven overnightto yield 2.66 g of solid. P-NMR showed the ratio of VPP:VPA to be 61:39in the polymer. The resultant was 88% polymer on a weight basis.

Example 29 Co-Polymerization of VPP with Methyl Acrylate

VPP (Example 1, 9.9 mmoles) and water, 4 mL, were charged in a roundbottom flask, and the headspace of the flask purged with flowingnitrogen for 15 minutes. The flask was sealed and heated to 60° C. for15 minutes to yield a homogeneous solution. Ammonium Persulfate (APS,225.7 mg) was dissolved in 1.2 g water. Every 30 minutes, 0.1 mL of theAPS solution and 0.073 mL Methyl Acrylate (Aldrich, 9.9 mmoles, 0.88 mLtotal) solution was added to the reaction over a total of 6 hours. At 3hours a milky white color began to form. The resultant was stirred 24hours at 60° C. yielding a milky white solution. Progress was monitoredby NMR and showed 20% remaining VPP at 24 hours and no remaining methylacrylate.

The reaction solution was added to 20 mL of additional water and 5 mL ofMeOH was then added over 5 minutes under rapid stirring. Resultant wasallowed to sit at room temperature for 10 minutes yielding a whiteprecipitate. The precipitate was filtered and the MeOH was removed fromthe filtrate.

The filtrate was diluted with 250 mL of water and dialyzed with 2Kmolecular weight cut off dialysis membranes against reverse osmosiswater for 5 days at a pH of approximately 6.5.

Water was removed from the product by freeze drying yielding 1.4 g whitesolid.

The phosphonate content in the polymers were determined by preparing anNMR sample with purified polymer & trimethyl phosphate (TMP) in D₂O. The¹H & ³¹P-NMR's were run from which the phosphonate content wascalculated from the H and P peaks of the internal standard (TMP)relative to the polymer peaks and water. Analysis showed the resultingpolymer to be 29% methyl acrylate, 16% Acrylate, 50% VPP, and 5% vinylphosphonate. The resulting solid was 77% polymer on a weight basis.

Example 30 Co-Polymerization of (4-VinylBenzyl) Phosphono-monoPhosphatewith SVS

(4-VinylBenzyl) Phosphono-monoPhosphate (VBPP, Example 5, 4.35 mmoles),bicarbonate (Aldrich 183 mg, 8.2 mmol) and SVS (Aldrich, 25% aqueoussolution, 8.1 mmoles), were charged in a round bottom flask, and theheadspace of the flask purged with flowing nitrogen for 15 minutes. Theflask was sealed and heated to 60° C. at which time a gas was evolved.Additional bicarbonate (total of 300 mg) was incrementally added untilno additional off gassing was observed. Ammonium Persulfate (APS,Aldrich, 284 mg, 10% relative to total monomers) was added in 0.5 mlwater. The resultant was stirred 24 hrs at 60° C.

¹H-NMR & ³¹P-NMR were run on the crude reaction solutions. The polymercomposition approximately 25/75 SVS/VBPP.

The crude reaction solution was diluted with 500 mL water and the pHadjusted to 8.5 with 1 N NaOH. This solution was dialyzed with 2Kmolecular weight cut off dialysis membranes against reverse osmosiswater for 6 days. Water was removed from the product by freeze dryingyielding 1.85 g white solid.

The phosphonate content in the polymers were determined by preparing anNMR sample with purified polymer & trimethyl phosphate (TMP) in D₂O. The¹H & ³¹P-NMR's were run from which the phosphonate content wascalculated from the H and P peaks of the internal standard (TMP)relative to the polymer peaks and water. The P-NMR shows broadphosphono-phosponate peaks at ˜13 to 15 ppm and −5 to −7 ppm inapproximately 1:1 ratio and also a phosphonate peak at ˜21-23 ppm. Basedon the ³¹P-NMR areas at 13-15 and 21-23 ppm, thephosphono-phosphonate:phosphonate ratio is 93:7. Based on this analysis,the polymer contained 30 mol % repeat units resulting from SVS, 65 mol %repeat units resulting from VBPP and 5 mol % repeat units resulting from(4-VinylBenzyl)Phosphonate. The water content was calculated to 18% on aweight basis.

Example 31 Co-Polymerization of (Phosphono-monoPhosphateEthyl)-Acrylamide with SVS

SVS, (Aldrich, 25% aqueous solution, 4.73 mmoles), was charged in around bottom flask, and the headspace of the flask purged with flowingnitrogen for 15 minutes. The flask was sealed and heated 10 to 60° C.Ammonium Persulfate (APS, Aldrich, 141 mg, 5% relative to totalmonomers) was added in 1.0 g water.Phosphono-monoPhosphate(Ethyl)-Acrylamide (Example 9, 4.95 mmoles) wasadded to 5.25 g water. To the flask with SVS, 0.1 mL APS solution and1.0 mL (Phosphono-monoPhosphate Ethyl)-Acrylamide was added every 20minutes for 3 hours. The resultant was stirred and additional 4 hours at60° C.

The crude reaction solution was diluted with 500 mL water and the pHadjusted to 8.5 with 1 N NaOH. This solution was dialyzed with 2Kmolecular weight cut off dialysis membranes against reverse osmosiswater for 6 days. Water was removed from the product by freeze dryingyielding 3.4 g tan solid. H-NMR & P-NMR were run on the crude reactionsolutions. The polymer composition is approximately 62:36:2SVS:(Phosphono-monoPhosphate Ethyl)-Acrylamide:(PhosphonateEthyl)-Acrylamide.

Example 32 Post Polymerization Modification of Co-Polymer of VPA and AA

The polymer from example 18 was esterified by refluxing 2.3 grams in 150mL of MeOH in a 250 mL 1 neck round bottom flask equipped with a heaterand magnetic stirring. After 1 hour of refluxing, a short pathdistillation head was added and approximately ⅓ of the MeOH was removed.This MeOH was then replace with fresh anhydrous MeOH a total of 4 times.This procedure yielded about 47% conversion to the methyl ester ofacrylic repeat units. Next, 2 drops of concentrated sulfuric acid wereadded and the solution was refluxed for 48 hours. This procedureincreased the total methyl ester content to 83% by H NMR. In addition,around 9% of the phosphonate esters were converted to mono-methylphosphonate esters by P NMR.

A magnetically stirred dry 50 ml 1 neck round bottom flask was chargedwith the methyl ester containing polymer (0.5, 1.63 mmole P) and 15 mlDMF under nitrogen. The resulting mixture was stirred overnight at roomtemperature yielding a swelled ball of polymer. Next, tributylamine(0.78 mL, 2.0 equivalents relative to P monomer) was added and stirredovernight at room temperature yielding a homogeneous solution. CDI (330mg, 1.25 equivalents relative to P monomer) and 5 mL DMF were premixedand added to solution. The resulting mixture was stirred overnightyielding a homogeneous solution.

H₃PO₄ (479 mg, 3 equivalents), tributylamine (1.26 mL 3.5 equivalent)and 5 mL of DMF were mixed and sonicated then added to the polymercontaining solution. Resultant was stirred overnight at roomtemperature. Resulting solution was stripped of solvent under vacuum (9Torr) to a final temperature of approximately 60° C.

The resultant was dissolved in 50 ml of 1 N NaOH yielding a solution atpH 13.15 and stirred overnight. Resultant was stripped of water withflowing dry nitrogen to yield a white paste. The paste was dissolved in60 mL of MeOH over 1 hour and the resulting solid collected and dried to2.52 grams. The crude solid was dissolved in water, pH adjusted to 9 andresulting solution dialyzed as described in previous examples. 0.67 g ofwhite fluffy solid was collected after lyophilization. P NMR showedaround 20% yield of phosphono-monophosphate groups from initialphosphonate groups.

Example 33 Co-Polymerization of (Phosphono-monoPhosphateEthyl)-Methacrylate with SVS

The procedure of example 31 was followed using 5.7 mmoles of SVS, and3.79 mmoles of (Phosphono-monoPhosphate Ethyl)-Methacrylate from Example7. After freeze drying, 1.5 g white solid was collected at 86% polymer,14% water/inactives. The polymer composition approximately 63:35:2SVS:(Phosphono-monoPhosphate Ethyl)-Methacrylate:(PhosphonateEthyl)-Methacrylate.

Example 34 Co-Polymerization of (PropylPhosphono-monoPhosphate)-Methacrylate with SVS

The procedure of example 31 was followed using 3.7 mmoles of SVS, and3.5 mmoles of (Propyl Phosphono-monoPhosphate)-Methacrylate from Example8. After freeze drying, 1.84 g white solid was collected at 86% polymer,14% water/inactives. The polymer composition approximately 56:44VSA:(Propyl Phosphono-monoPhosphate)-Methacrylate.

Example 35 Post Polymerization Modification of Homopolymer of VPA

Poly(vinylphosphonic acid) (500 mg) was added to a 100 ml round bottomflask followed by methanol (20 ml). Tributylamine (1.1 mL) was added tothe mixture and stirred for 30 minutes and the mixture becamehomogeneous. Resulting solution was concentrated under vacuum followedby the addition of pyridine (10 mL) and removal under vacuum threetimes. Resulting solid was dissolved in 10 mL pyridine. Diphenylphosphoryl chloride (956 μL, 1 equivalent) was slowly added however, aprecipitate formed in the reaction mixture so it was diluted withadditional pyridine (50 ml). After 1 hour mono(tributylamine) phosphatewas added (3.3 mL, 3 equivalents) and this was stirred overnight.

Solvent was removed under vacuum and the resulting solid was dissolvedin water and dialyzed. After dialysis the water was removed via freezedrying to yield a sticky solid. PNMR analysis indicated 87.7% of thephosphonates had for an anhydride with an adjacent phosphonate, while12.3% were phosphono-monophosphate.

Example 36 Post Polymerization Modification of PolyMethyl-VinylPhosphonate

Following a similar procedure to Example 32 a magnetically stirred dryround bottom flask is charged with poly methyl-vinyl phosphonate, DMFand purged with nitrogen. Next, tributylamine (2.0 equivalents relativeto P monomer) is added and stirred overnight at room temperatureyielding a homogeneous solution. CDI (1.25 equivalents relative to Pmonomer) and DMF are premixed and added to solution which is stirredovernight. H₃PO₄ (3 equivalents), tributylamine (3.5 equivalent) and DMFare mixed and sonicated then added to the polymer containing solution.Resultant is stirred overnight at room temperature. Resulting solutionis stripped of solvent under vacuum (9 Torr) to a final temperature ofapproximately 60° C. to yield a phosphono-phosphate containing polymer.

Example 37 Post Polymerization Modification of Random PhosphonateContaining Polymer

Phosphonated polyethylene is synthesized by following the description ofAnbar (M. Anbar, G. A. St. John and A. C Scott, J Dent Res Vol 53, No 4,pp 867-878, 1974) or Schroeder and Sopchak (J, P. Schroeder and W. P.Sopchak, Journal of Polymer Science Volume 47 Issue 149 p 417 (1960)).Briefly 10 g polyethylene is reacted in a dry flask with 200 g of PCl₃at reflux until the polymer dissolves. Next dry oxygen is flowed throughthe dissolved solution. Resulting solution is distilled to reduce theoverall volume by half and is poured over ice chips to createphosphonated polyethylene. This phosphonated polyethylene is reactedfollowing the procedure of Example 36.

Example 38 Post Polymerization Modification ofPoly(vinylbenzylphosphonic acid) Containing Polymer

Poly(vinylbenzylphosphonic acid) is synthesized by polymerizing(4-VinylBenzyl) Phosphonic Acid using either heat in methanol asdescribed by Anbar et al. or by using an initiator such as ammoniumpersulfate at 5-10% loading relative to monomer. The resulting polymeris reacted following the procedure of Example 36.

Example 39 Synthesis of a Phosphono Phosphate Monomer and Polymer on aSide Chain

The procedure of Example 12 is followed substituting an ethylene glycoldimer, trimer, tetramer or polymer with a primary hydroxy group such asdiethyl (2-hydroxyethoxy)ethoxy)ethyl)phosphonate for dimethyl(2-hydroxyethyl)phosphonate. Ethyl phosphonate terminated ethyleneglycol units can be synthesized by following the procedure of Brunet etal. (Ernesto Brunet,* Marn'a Jose'de la Mata, Hussein M. H. Alhendawi,Carlos Cerro, Marina Alonso, Olga Juanes, and Juan CarlosRodri'guez-Ubis Chem. Mater. 2005, 17, 1424-1433). Briefly, the desiredethylene glycol dimer, trimer, tetramer or polymer (1 equivalent) isadded over 2-4 days to a 90° C. mixture of Cs₂CO₃ (1.2 equivalents)diethylvinylphosphonic acid (12.5 equivalents). Purification isperformed by extracting with water dichloromethane followed by flashchromatography. Polymerization of the phosphono-phosphate containingmonomer is performed as described in Example 22 to yield a homopolymeror with co-monomers as described in Examples 19, 20, 23, 24, 25, or 26to yield co-polymers.

Example 40 Synthesis of a Phosphono Phosphate Polymer on a Side Chain byPost-Polymerization Modification

Ethoxylated polyvinyl alcohol is reacted as described in Example 38 tocreate a phosphonate terminated ethoxylated polyvinyl alcohol polymer.Ethoxylated polyvinyl alcohol is synthesized by reacting polyvinylalcohol in a sealed reactor at a temperature of 85-120° C. and apressure of 20-200 psig with a base catalyst such as methoxide or sodiumhydroxide and ethylene oxide added slowly over several hours. Thisphosphonate terminated polymer is reacted as described in Example 36 tocreate a phosphono-phosphate containing polymer where thephosphono-phosphate is attached to a side chain of the polymer bypost-polymerization modification.

Example 41 Co-Polymerization of di-Methyl Vinyl Phosphonate (DMVP) withSVS

SVS (Aldrich, 25% aqueous solution, 11.0 mmoles) was charged in a roundbottom flask, and the headspace of the flask purged with flowingnitrogen for 15 minutes. The flask was sealed and heated to 60° C. for15 minutes. Ammonium Persulfate (APS, 225 mg) was added in 1.0 g water.Every 30 minutes, 0.1 mL of the APS solution and 0.1 mL of DMVP(Aldrich, 1.5 g, 1.3 mL, 11.0 mmoles) were added to the reaction over atotal of 6 hours. The resultant was stirred 24 hrs at 60° C.

The crude reaction solution was diluted with 250 mL of water anddialyzed with 2K molecular weight cut off dialysis membranes againstreverse osmosis water for 4 days. The initial pH of the dialysis waterwas 5.8 but dropped to 2.5.

Water was removed from the product by freeze drying yielding 2.4 g whitesolid.

Based on NMR analysis the polymer contained 56.9 mol % repeat unitsresulting from SVS, 43.1 mol % DMVP. The water content was calculated to10.4% on a weight basis.

Example 42 Co-Polymerization of Example 23 Co-Polymerization of (EthylPhosphono-monoPhosphate)-Vinyl Ether and (AMPS)

(Ethyl Phosphono-monoPhosphate)-Vinyl Ether (Example 11, 4.7 mmoles),water 5 mL, and AMPS (4 g of 50% solution, 8.7 mmoles) were charged in around bottom flask, and the headspace of the flask purged with flowingnitrogen for 15 minutes. The flask was sealed and heated to 60° C. for15 minutes to yield a homogenous solution. Ammonium Persulfate (APS, 306mg) was dissolved in 1.1 g water. Every 30 minutes, 0.1 mL of the APSsolution was added to the reaction over a total of 4 hours. Theresultant was stirred 4 hours at 60° C.

The crude reaction solution was diluted with 750 mL of water anddialyzed with 2K molecular weight cut off dialysis membranes againstreverse osmosis water for 8 days.

Water was removed from the product by freeze drying yielding 2.12 g tansolid.

Based on NMR analysis, the polymer contained 90.8 mol % repeat unitsresulting from AMPS, 9.2 mol % repeat units resulting from (EthylPhosphono-monoPhosphate)-Vinyl Ether. The solid was found to contain 77%water by weight.

Example 43 PSPM on VPA SVS Co Polymers

The polymers from Example 17 were tested according the PSPM model alongwith homopolymers of Poly Vinyl Sulfonate and Poly Vinyl phosphonatepurchased from PolySciences Inc. Results are shown in FIG. 1 and Table 3(below) along with pyrophosphate and polyphosphate.

TABLE 3 Source/Name % S % P Delta L PolyScience 100%   0% 16.3 Example17 80% 20% 8.7 Example 17 69% 31% 9.0 Example 17 57% 43% 6.0 Example 1756% 44% 6.7 Example 17 44% 56% 9.3 Example 17 34% 66% 12.9 PolyScience 0% 100%  15.8 Pyrophosphate 16.3 Polyphosphate 2.0

Example 44 PSRM on VPA SVS Co Polymers

The polymers from Example 17 were tested according the PSRM model alongwith homopolymers of Poly Vinyl Sulfonate and Poly Vinyl phosphonatepurchased from PolySciences Inc. Results are shown in FIG. 2 and Table 4(below) along with pyrophosphate, polyphosphate and the water treatment.

TABLE 4 % Sulfonate % Phosphonate Source/Name in Polymer in PolymerDelta L PolyScience 100.0%    0% 23.1 Example 17 80% 20% 24.2 Example 1769% 31% 23.5 Example 17 57% 43% 22.4 Example 17 56% 44% 21.9 Example 1744% 56% 23.2 Example 17 34% 66% 22.2 PolyScience 0.0%  100%  21.6Pyrophosphate 14.2 Polyphosphate 9.2 Water Blank 25.0

Example 45 PSPM on VPP SVS Co Polymers

The polymers from example 20 were tested according the PSPM model.Results are shown in FIG. 3 and Table 5 (below) along with pyrophosphateand polyphosphate.

TABLE 5 % Phosphono- % Sulfonate % Phosphonate Phosphonate Source/Namein Polymer in Polymer in Polymer Delta L Example 20 81% 4% 15% 5.9Example 20 79% 1% 20% 4.8 Example 20 67% 3% 30% 3.0 Example 20 62% 3%35% 1.6 Example 20 66% 3% 30% 5.2 Example 20 56% 2% 42% 2.7Pyrophosphate 16.3 Polyphosphate 2.0

Example 46 PSRM on VPP SVS Co Polymers

The polymers from example 20 were tested according the PSRM model.Results are shown in FIG. 4 and Table 6 (below) along withpyrophosphate, polyphosphate and the water treatment.

TABLE 6 % Phosphono- % Sulfonate % Phosphonate Phosphonate Source/Namein Polymer in Polymer in Polymer Delta L Example 20 79% 1% 20% 16.2Example 20 67% 3% 30% 13.9 Example 20 62% 3% 35% 13.3 Example 20 56% 2%42% 12.6 Pyrophosphate 14.2 Polyphosphate 9.2 Water Blank 25.0

Example 47 PSRM and PSPM on Mixed Co Polymers

The polymers from previous examples as noted below were tested accordingthe PSRM and PSPM models. Results are shown in Table 7 below along withpyrophosphate, polyphosphate and the water treatment.

TABLE 7 Compound Structure PSRM PSPM Example 29

11.0 10.5 Example 22

10.9 8.0 Example 28

12.9 7.1 Example 30

17.1 22.9 Example 6

20.7 29.8 Example 31

17.8 17.1 Example 33

16.3 17.4 Example 23

13.3 10.1 Example 41

24.7 16.4 Example 24

11.7 9.2 Example 21

18.0 5.8 Example 25

12.9 11.6 Example 26

15.8 8.9 Example 42

15.8 19.2 Example 27

21.2 18.3 Example 34

6.4 11.7 Water Control 26.8-30.0 25.0-29.0 2% Pyro 13.0-18   12.2-16.02% GlassH  3.5-11.0 3.0-8.6 HAP blank 0.0 0.0

General Chemical Scheme for Examples 48-52—Synthesis of VinylPhosphono-monoPhosphate (VPP) or [vinylphosphonic phosphoric anhydride]and Other Extended Vinyl Phosphono-Phosphates (eVPP) by Removal of Water

The following chemical scheme shows general reaction scheme in examples48-52 used to form the primary desired products, VPP and VPPP, alongwith some of the other products observed in some but not all of thefollowing experiments. Please refer to individual examples for finalidentified product distributions.

Example 48—Synthesis of VPP and eVPP by Evaporation Using a Sweep Gaswith 3 Equivalents of PA

A 50 mL 3 neck round bottom flask, equipped with a magnetic stirrer anda short path distillation head in the middle neck, was charged with 1gram of vinyl phosphonic acid (VPA) and 2.72 g (3 equivalents) of 99%phosphoric acid (PA). One side neck was stoppered, and nitrogen wasswept through the other side neck and out through the distillation head.The flask was placed in oil bath heated to 105° C. and stirred at thattemperature for 27 hours. Samples (˜1 drop) were removed at desired timepoints, dissolved in 1 mL D7-DMF with 0.25 mL tributyl amine, andevaluated by P-NMR. The final product was found to contain VPA,Vinyl-Phosphono-monoPhosphate (VPP), Vinyl-Phosphono-Pyrophosphate(VPPP), Vinyl-Phosphonic Acid Anhydride (VPPV), Phosphoric acid (PA),Pyrophosphoric Acid (PP) & Tri-Phosphoric Acid (PPP). Speciesidentification was confirmed using LCMS. In addition H-NMR was run onthe final 27 hour sample from which it was determined that nopolymerization occurred during the reaction.

Final molar distributions of all vinyl containing species in the melt at27 hours was found to be 43% VPA, 38% VPP, 9% VPPP, and 10% VPPV.

Example 49—Synthesis of VPP and eVPP by Evaporation Using Vacuum and aSweep Gas with 3 Equivalents of PA

The procedure of example 48 was followed with the following changes. Theshort path distillation head was connected to a Buchi vacuum pump ratherthan venting to atmosphere. The round bottom flask was evacuated to50-60 Torr for the duration of the experiment with constant flow ofnitrogen from one side neck. Sampling at 32 and 48 hours showed littlechange between the time points with a vinyl containing distribution of31-32% VPA, 40-41% VPP, 14% VPPP, and 13-14% VPPV. Signals correspondingto VPPPV were also observed in P-NMR but were not quantified do tooverlap with other peaks.

Example 50—Synthesis of VPP and eVPP by Evaporation Using Vacuum and aSweep Gas with 6 Equivalents of PA

The procedure of example 49 was followed with 6 equivalents of PArelative to VPA. The distribution of vinyl containing species at 72hours was 31% VPA, 40% VPP, 21% VPPP, and 8% VPPV. Signals correspondingto VPPPV were also observed in P-NMR but were not quantified do tooverlap with other peaks.

Example 51—Synthesis of VPP and eVPP by Reaction with PhosphorousAnhydride (P₂O₅, Phosphorous Pentoxide)

To a magnetically stirred 20 mL scintillation vial was added 2.24 g of85 weight % phosphoric acid in water, 1.01 g 90% vinyl phosponic acidand 2.5 phosphorous pentoxide (in that order). The molar ratio of vinylphosphonate to total phosphate (calculated as the sum of the moles ofphosphate plus twice the moles of P₂O) as 6. The vial was heated to 175°C. and sampled for P NMR at 1 hour using the procedure of example X. Themolar composition of identified vinyl containing species was 34% VPA,41% VPP, 19% VPPP and 5% VPPV. Additional vinyl peaks were visible in PNMR that likely correspond to larger species including VPPPP, andVPPPPP. LCMS confirmed the existence of higher orderphosphono-phosphates with peaks for VPP, VPPP, VPPPP, VPPPPP, VPPPPPP,and VPPPPPPP all visible in negative ion mode.

Example 52—Scale up and Purification of Example 49

The procedure of example 49 was followed with a 5-fold increase in totalmaterials. Sampling at 32 hours showed a distribution of vinylcontaining species of 35% VPA, 37% VPP, 12% VPPP, 12% VPPV and 4% VPPPV.

After cooling, the bulk of the crude reaction mixture was dissolved in40 ml anhydrous DMF. The dissolved solution was added to a solution of28.1 g triethyl amine (1.5 equivalents based on total starting acid) in100 mL of anhydrous DMF with rapid stirring over 5 min. The P-NMR wasrun on the resultant solution and was consistent with distributions fromthe crude reaction mixture.

The resultant solution was stripped of DMF at 70° C. & 25 Torr yielding38.4 g viscous yellow oil. This was dissolved in 100 mL H₂O yielding asolution with a pH of 2.5, which was adjusted to 11.0 with 110 g 10%NaOH yielding a clear solution. The P-NMR was run on the resultantsolution which showed a consistent product distribution as previoussamples, but with an approximate 20% reduction in VPPV. Upon standing atroom temperature for 1 hour, a white precipitant formed which wascollected by filtration, dried overnight in ambient air to 4.65 g Thisprecipitant was found to be about 90% pyrophosphate, with 4% phosphateand less than 3% each of VPA, VPP and PPP. The filtrate was stripped ofsolvent yielding 49.4 g clear viscous oil. The pH of the resultant oilwas checked by litmus and found to be around 7. This was brought up toapproximately 125 g with additional water yielding a pH of 7.5 which wasadjusted to 11.0 with 15.2 g 1N NaOH. To this pH 11 solution was added250 ml MeOH with rapid stirring over 30 min. at room temperature. Awhite precipitant formed over the course of one hour. This precipitantwas collected by filtration, rinsed one time with 50 mL 2:3 H2O:MeOH anddried under ambient air overnight to 17.9 g. This precipitant was foundto be approximately 43% pyrophosphate, 39% phosphoric acid, 10% PPP, 3%VPP and 4% VPPP. The MeOH water solution was concentrated under flowingnitrogen overnight at room temperature to yield 31.1 g of viscous oil.The oil was found to have a molar phosphorous distribution ofapproximately 33% VPA, 33% VPP, 8% VPPP, 11% PA, 10% VPPV and 3% VPPPV.The oil was also found to have residual water and DMF.

To the oil, 300 ml MeOH was added over 1 hr at room temperature yieldinga white precipitant which was collected by filtration, rinsed 1×50 mLMeOH and dried under vacuum at room temperature for 2 hrs to yield 4.3 gwhite powder. The powder was found to have a molar phosphorousdistribution of 49% VPP, 26% PA, 6% PP, 15% VPPP and 3% VPA. The MeOHsolution was concentrated under flowing nitrogen at room temperature 7.0g white paste. The composition of the white paste was found to beapproximately 73% VPA, 23% VPP and 5% VPPPV.

Example 53—Polymerization to Create VPPP Containing Polymer and Testingwith PSPM and PSRM

The white powder from example 52 containing 49% VPP, 26% PA, 6% PP, 15%VPPP and 3% VPA, was polymerized following the procedure of Example 19and 20 using a 50/50 mixture (total molar vinyl basis) of the white VPPPcontaining powder (8.6 mmol vinyl groups) and SVS (8.6 mmol vinylgroups). After dialysis and freeze drying, 3.6 g of polymer wascollected and found to contain 57% monomers based on SVS, and 43% basedon phosphonates. The phosphonate distribution was 3% from VPA, 78% fromVPP and 18% from VPPP. The polymer was 78% active on a weight basis with22% impurities/water. This polymer was tested in the PSPM and PSRMmodels with values of ΔL of 5.5 and 11.0 respectively. The controls forthe PSPM were: Water 28.0, HAP Blank 0.0, Pyrophosphate 18.0,Polyphosphate 4.0, and the controls for the PSRM were: Water 24.2, HAPBlank 0.0, Pyrophosphate 12.4 Polyphosphate 8.6.

Examples 54-57—Scale Up and Testing in Oral Care Formulations

The following examples demonstrate formulation of the polymerscontaining phosphono-phosphates into a dentrifice and subsequent testingin the stain models.

Example 54—20-30 g Scale up of Example 19 and 20

The procedure of examples 19 and 20 was scaled up using 96.7 mmoles ofVPP and 96.7 mmoles of VSA with an equivalent increase of other reagentsand solvents. After dialysis and freeze drying, 27.1 g of polymer wascollected and found to contain 59% monomers based on SVS, 40% based onVPP and 2% based on VPA. The polymer was 83% active on a weight basiswith 17% impurities/water.

This polymer was tested in the PSPM and PSRM models with values of ΔL of6.8 and 13.0 respectively. The controls for the PSPM were: Water 28.0,HAP Blank 0.0, Pyrophosphate 14.3, Polyphosphate 3.1, and the controlsfor the PSRM were: Water 25.0, HAP Blank 0.0, Pyrophosphate 13.5,Polyphosphate 10.7.

Example 55—20-30 g Scale Up of Example 16 and 17

The procedure of examples 16 and 17 was scaled up using 148 mmoles ofVPP and 122 mmoles of VSA with an equivalent increase of other reagentsand solvents. After dialysis and freeze drying, 26.8 g of polymer wascollected and found to contain 54% monomers based on SVS, 46% based onVPA. The polymer was 90% active on a weight basis with 10%impurities/water. This polymer was tested in the PSPM and PSRM modelswith values of ΔL of 10.2 and 20.2 respectively. The controls for thePSPM were: Water 28.0, HAP Blank 0.0, Pyrophosphate 14.3, Polyphosphate3.1, and the controls for the PSRM were: Water 25.0, HAP Blank 0.0,Pyrophosphate 13.5, Polyphosphate 10.7.

Example 56-100 g Scale Up of Example 19 and 20

The procedure of examples 19 and 20 was scaled up using 354.5 mmoles ofVPP and 433 mmoles of VSA with an equivalent increase of other reagentsand solvents. After neutralization the bulk solution was brought up to9819 g with water and pH adjusted to 10 with 1N NaOH. Low MW impuritieswere reduced in the resultant solution by Tangential Flow Filtration(TFF) using Tami Industries 1000 MWCO column (E190613N001). The solutionwas pumped from a reservoir through the column and back into thereservoir. The effluent that passed through the pores of the column wascollected in a flask on a balance. In the first run, the solution waspumped until 3.5 kg of effluent was collected. The remaining solution inthe reservoir was then brought back up to around 9 kg. The procedure wasrepeated with 4.8 kg removed and the reservoir brought up to 11 kg. Inthe final run, 6 kg of effluent was removed. After the final TFF theconcentrated solution was filtered thru a 0.22 μm filter (Stericup 500ml Filter Unit, Aldrich).

The water was removed from the final TFF concentrate after filtering byevaporation under flowing nitrogen for for 5 days at room temperatureyielding 173 g tan paste. This was further dried under vacuum at >1 Torrfor 48 hours yielding 137.2 g light tan solid. The solid was found tocontain 66% monomers based on SVS, 34% based on VPP. The polymer was 80%active on a weight basis with 20% impurities/water. This polymer wastested in the PSPM and PSRM models with values of ΔL of 6.5 and 11.5respectively. The controls for the PSPM were: Water 28.0, HAP Blank 0.0,Pyrophosphate 18.0, Polyphosphate 4.0, and the controls for the PSRMwere: Water 24.2, HAP Blank 0.0, Pyrophosphate 12.4 Polyphosphate 8.6.

Example 57—Formulation and Testing of Examples 54-56

All percentages in this example are by weight unless otherwise noted.

The compositions were prepared as follows:

Composition #1 was commercially purchased Crest Cavity ProtectionRegular Flavor.

Composition #2 was commercially purchased Crest ProHealth Clean MintSmooth Formula.

Composition #3 is the same as Composition #2 with the addition ofPolymer Example 54.

Composition #2 was weighed into a Speedmix jar. The polymer Example 54was then added to the Speedmix jar and mixed in a Speedmixer untilhomogeneous. The pH was then determined with a pH electrode and 2N HClwas added and mixed in a Speedmixer to adjust the pH to a target of ˜6.

Composition #4 is the same as Composition #2 with the addition ofPolymer Example 55. Composition #2 was weighed into a Speedmix jar. Thepolymer Example 55 was then added to the Speedmix jar and mixed in aSpeedmixer until homogeneous. The pH was then determined with a pHelectrode and 50% NaOH solution was added and mixed in a Speedmixer toadjust the pH to a target of ˜6.

Composition #5 was prepared in a pilot scale mixer by addingapproximately half of the sorbitol to the mixer, heating to 65° C. witha heating/cooling jacket on the tank and pulling vacuum. In a separatecontainer 1 weight percent of the silica and all the hydroxyethylcellulose were dry blended until homogeneous and then drawn by vacuuminto the mixing vessel. A both an anchor agitator and high shearrotor/stator device were used to mix and homogenize the mixture toassure homogeneity and hydration of the hydroxyethyl cellulose. Oncehomogeneous, the rotor/stator device was turned off. The remainingsorbitol, about 25% of the water and all the blue dye were added andmixed until homogeneous using the anchor agitator. In a separatecontainer, 1 weight percent of the silica, all the saccharin and all thecarrageenan were dry blended and drawn into the main mix vessel undervacuum with the high shear rotor/stator device and anchor agitatorrunning. Once homogenous, the rotor/stator was turned off. Next theremaining silica was drawn into the main mix vessel under vacuum andmixed using the achor agitator at a vacuum not less than 26 inches ofmercury. The batch was then cooled to approximately 49° C. via theheating/cooling jacket while continuing to be mixed with the anchoragitator. Once the batch reached 49° C., the achor agitator was stopped,the mixer was opened and the flavor and sodium lauryl sulfate solutionwere added to the top of the batch. Vacuum was then pulled to 24 inchesof mercury and the anchor agitator and rotor/stator were turned on untilthe batch was homogeneously mixed. After mixing, the rotor/stator wasturned off and vacuum was pulled to 27 inches of mercury to remove air.In a separate container, the remaining 75% of the water was heated to 65C. Sodium gluconate was added to the water and mixed until dissolved.Stannous fluoride was then added to the gluconate solution and mixeduntil dissolved. Stannous chloride was then added to the gluconatesolution and mixed until dissolved. Once this solution was prepared, itwas added under vacuum to the main mix vessel and mixed using the anchoragitator until homogeneous. After the mixing, the sodium hydroxide wasadded under vacuum to the main mix vessel and the anchor agitator androtor/stator were used to mix homogeneously. Once homogeneous, therotor/stator was turned off and the heating/cooling jacket was reducedto 30° C. and vacuum was pulled to 26 inches of mercury. The batch wasmixed under vacuum until the temperature reached 35° C., it was pumpedout of the main mix vessel.

Composition #6 is the same as Composition #5 with the addition ofPolymer Example 56. Composition #5 was weighed into a Speedmix jar. Thepolymer Example 56 was then added to the Speedmix jar and mixed in aSpeedmixer until homogeneous. The pH was then determined with a pHelectrode and no further adjustment was needed to achieve a pH of ˜6.

Composition #7 is the same as Composition #2 with the addition ofPolymer Example 56. Composition #2 was weighed into a Speedmix jar. Thepolymer Example 56 was then added to the Speedmix jar and mixed in aSpeedmixer until homogeneous. The pH was then determined with a pHelectrode and 50% NaOH solution was added and mixed in a Speedmixer toadjust the pH to a target of ˜6.

Composition #5 Formula #2 Composition #1 Composition #2 Composition #3Composition #4 Nil Polymer Composition #6 Composition #7 iPTSM NegativeFormula #1 Formula #1 Formula #1 (iPTSM Positive Formula #2 Formula #1Control Nil Polymer w/Example 54 w/Example 55 Control) w/Example 56w/Example 56 H2O 11.165 21.156 20.599 20.719 13 12.684 20.492 NaF 0.243SnF2 0.454 0.442 0.445 0.454 0.443 0.44 NaOH (50%) 0.87 0.847 0.881 0.80.781 0.843 Sorbitol 65.508 48 46.737 47.009 55.159 53.819 46.493Monosodium 0.419 Phosphate dihydrate Trisodium 1.1 PhosphateDodecahydrate Carboxy 0.75 Methyl Cellulose Carbomer 956 0.3 Z119 150.056 0.055 0.055 20 19.514 0.054 Z109 17.5 17.039 17.139 0 0 16.951TiO2 0.525 0.5 0.487 0.49 0.25 0.244 0.484 Carrageenan 1.5 1.461 1.4690.8 0.781 1.453 Xanthan Gum 0.875 0.852 0.857 0 0 0.848 Hydroxyethyl 00.5 0.488 0 Cellulose Sodium Lauryl 4 5.00 4.868 4.897 4 3.903 4.843Sulfate (29% Sol'n) Saccharin 0.13 0.45 0.438 0.441 0.455 0.444 0.436Flavor 0.81 1.30 1.266 1.273 1 0.976 1.259 ZnCitrate 0.53 0.519 0.522 00 0.516 NaGluconate 1.30 1.266 1.273 2.082 2.031 1.259 SnCl2*2H2O 0.510.492 0.495 1.5 1.464 0.49 2N HCl 0.28 0.277 0 0 0.726 Dye Solution 0.05Example 54 2.35 2.355 0 0 0 (VSA/VPP) Example 55 0 0 2.036 0 0 (VSA/VPA)Example 56 0 2.43 2.412 (VSA/VPP) Total 100 100 100 100 100 100 100 PSPM(ΔL/ΔE)  24.3/31.07 19.47/27.84  6.79/10.34 12.62/18.10 30.91/43.9120.15/30.80  7.02/10.64 PSRM (ΔL/ΔE) 19.47/24.72 18.15/24.55 18.38/25.3116.96/22.71 21.02/30.71 19.95/27.69 17.39/22.31 iPTSM % Stain 0% 3% −41%−49% 100% — — Potential

Example 58—Synthesis of VPP and eVPP by reaction with Phosphoric Acidand Urea

For all samples in the example, the following general procedure wasfollowed:

A scintillation vial was charged with VPA, 85% or 99% H₃PO₄, urea &water as noted in the Table 1 below. The resultant was stirred at 60° C.for approximately 15 minutes until a homogenous solution was obtained.The resultant solution was transferred hot into an 800 mL beaker. Thiswas placed in a programmable lab oven with circulating air flow andexterior ventilation. All samples were heated as follows:

1) Ramped from room temperature to 110° C. over 15 minutes.

2) Hold at 110° C. 3 hours.

3) Ramped from 110° C. to 150° C. over 15 minutes.

4) Hold at 150° C. for either 15 or 60 minutes as noted in table below.

5) Cooled to room temperature and allow to stand overnight.

P-NMR was run on the crude reaction products (˜50 mg reaction product in1 mL D₂O with 5 drops 30% NaOD). The products were found to contain VPA,vinyl-phosphono-phosphate (VPPA), vinyl-phosphono-pyrophosphate (VPPPA),vinylphosphonic anhydride (SM-An), phosphoric acid (PA), pyrophosphoricacid & tri-phosphoric acid (PPP). Areas from P-NMR are shown in Table 3below. H-NMR's were also run on the reaction products to check forpolymerization of the VPA during the heating. No polymer was observed.

TABLE 3 % Areas from P NMR Sample Prep & Rx Conditions Rx VPPA + g g g gEquiv Equiv Equiv Time # VPA VPPA VPPPA SM-An VPPPA VPA H2O H3PO4/% UreaVPA H3PO4 Urea 150 C. 1 46.9 22.7 5.0 25.4 27.7 0.5 1.5 0.58 g 85% 0.331 1.1 1.2 15 min 1 48.9 29.5 7.1 14.4 36.6 0.5 1.5 1.16 g 85% 0.66 1 2.22.4 15 min 3 33.4 38.5 13.4 14.8 51.8 0.5 1.5 1.75 g 85% 1 1 3.3 3.6 15min 4 36.4 40.2 15.7 7.6 56.0 0.5 1.5 3.48 g 85% 2 1 6.6 7.2 15 min 5100.0 0.0 0.0 0.0 0.0 0.5 1.5 3.48 g 85% 0 1 6.6 0 15 min 6 33.1 38.119.2 9.6 57.3 0.5 0 2.95 g 99% 2 1 6.6 7.2 15 min 7 48.5 34.3 10.5 6.744.8 0.5 1.5 3.48 g 85% 2 1 6.6 7.2 60 min 8 45.8 36.2 11.1 6.9 47.3 0.50 3.48 g 85% 2 1 6.6 7.2 60 min 9 54.7 29.5 7.4 8.4 36.9 0.5 0 1.75 g85% 1 1 3.3 3.6 60 min 10 54.1 32.1 8.3 5.5 40.4 0.5 0 2.95 g 99% 2 16.6 7.2 60 min 11 32.1 38.1 21.9 7.8 60.1 0.5 0 3.48 g 85% 2 1 6.6 7.215 min 12 41.7 32.4 14.0 11.9 46.4 0.5 0 1.75 g 85% 1 1 3.3 3.6 15 min13 33.0 36.5 22.0 8.5 58.5 0.5 0 2.95 g 99% 2 1 6.6 7.2 15 min 14 40.229.6 17.0 13.2 46.6 0.5 0 3.48 g 85% 4 1 6.6 14.4 15 min 15 42.7 25.722.7 8.9 48.4 0.5 0 1.75 g 85% 2 1 3.3 7.2 15 min

Example 59—Synthesis of Polymer Containing VPP and eVPP by Reaction ofPolymer with Phosphoric Acid and Urea

Dimethyl vinyl phosphonate, DMVP (10.6 g, 77.9 mmoles) and sodium vinylsulfonate solution, SVS (25% aqueous solution, 40.5 g, 77.9 mmoles),were charged in a 100 mL round bottom flask. The flask was purged withnitrogen for 15 minutes and heated to 60° C. Ammonium persulfate APS,888 mg, 2.55% of total monomer, was brought up in 4 g of water anddegassed with nitrogen for 5 minutes. The APS solution was added to thesolution containing DMVP and SVS and resultant solution was allowed tostir for 24 hours under nitrogen at 60° C.

¹H-NMR & ³¹P-NMR were run on the crude reaction solution, and a monomerconversion of around 99% was observed with a broad P polymer peak at ˜37ppm from the phosphonate group.

The crude reaction solution was diluted to 10 wt % polymer in water with207 g of water. To this was added 300 mL of acetone over 30 minutesunder continuous stirring at room temperature to yield a turbidsolution. After standing in a separatory funnel for 30 minutes a lowerviscous polymer rich syrup and upper fluid organic layer were formed.The lower layer was collected, solvent evaporated under nitrogenovernight followed by vacuum, 2 hours at 1 Torr to yield 15.3 grams of atacky tan solid. ¹H-NMR & ³¹P-NMR were run on this solid with aninternal standard, trimethyl phosphate, to show a 50:50 ratio ofDMVP:SVS derived groups.

The tacky tan solid was mixed with 30 grams of water and 45 grams ofconcentrated HCl (≈37%) to yield a milky white solution. This mixturewas refluxed for 48 hours to yield a transparent solution with a slightbrown color. The water and HCl were stripped from the solution on aroto-vap operating at 60° C. and 20 torr to a total volume of ≈20 mL.100 additional mL of water was added to this remaining fraction and thestripping was repeated, then 200 mL of water was added, the sample wasfrozen and lyophilized to yield 11.8 g of tan solid. ³¹P-NMR showed ashift in the polymer beak from ≈37 to ≈32 ppm, while the ¹H-NMR showedthe disappearance of the peak polymer peak at ≈3.8 ppm that correspondedto the methyl ester peak. Analysis with an internal standard indicated aratio of P containing groups to sulfur containing groups ofapproximately 47 to 53, and a weight activity of 82.4%

A 100 mL beaker was charged with 4.85 grams of 85% phosphoric acid and2.77 grams of urea and heated to 60° C. for 15 minutes then cooled toroom temperature to yield a clear solution. 5 grams of 82.4% activepolymer with a calculated ratio of P to S of 47 to 53 was dissolved in15 mL of water and this was added to the phosphoric acid/urea mixture inthe 100 mL beaker. This was placed in a programmable lab oven withcirculating air flow and exterior ventilation and heated as follows:

1) Ramped from room temperature to 110° C. over 15 minutes.

2) Hold at 110° C. 3 hours.

3) Ramped from 110° C. to 150° C. over 15 minutes.

4) Hold at 150° C. for 15 minutes.

5) Cooled to room temperature and allow to stand overnight.

11.4 grams of spongy white product was collected. P-NMR was run on thecrude reaction products (˜150 mg reaction product in 1 mL D₂O with 2drops 30% NaOD). P-NMR demonstrated a broad peak at ≈−5 ppmcorresponding to a phosphono-phosphate group on a polymer chain. Aportion of this peak is overlapped by pyrophosphate makingquantification difficult.

The bulk of the crude, 11.4 g, was dissolved in 50 mL of water, chargedto a round bottom flask under stirring and 50 mL of methanol added over30 minutes to yield a turbid solution. Upon standing in a separatoryfunnel for 30 minutes, a lower viscous polymer rich syrup layer resultedwhich was separated (9.5 g). The ratio of polymer to phosphate topyrophosphate was evaluated by P-NMR and found to be 161 to 43 to 113.

The precipitation was repeated on the above 9.5 grams of syrup using 50mL of water and 50 mL of methanol. 2.13 g syrup resulted. P-NMR showedthe polymer to phosphate to pyro ratio to be 158 to 3 to 18.

The resultant syrup was brought up to 250 mL of reverse osmosis (RO)water further purified by dialysis in a Thermo Scientific Slide-A-Lyzerdialysis flask (2K MWCO) against RO water (pH adjusted to 8.5 w satsodium bicarbonate solution) for 6 days. The water was removed byfreezing and lyophilization yielding 1.59 grams white solid. ¹H-NMR &³¹P-NMR showed the collected polymer to be ≈41% P monomers, and 59% Smonomers. Analysis of the P containing groups showed ≈22%phosphono-phosphate groups with a small amount ofphosphono-pyrophosphate groups. The remaining P containing groupsappeared to be a mixture of phosphonate and phosphonate anhydridestructures. The polymer was calculated as 87.4% weight active.

Example 60 Co-Polymerization of Vinyl Phosphono-monoPhosphate (VPP) andSodium Vinyl Sulfonate (SVS) with Purification

VPP (made on larger scale as described in Example 1, 64.6 g active, 254mmoles) and SVS (25% aqueous solution, 161.6 g, 310 mmoles), initialmolar ratio of SVS to VPP of 55 to 45, were charged in a 500 mL roundbottom flask, stirred and the headspace of the flask purged with flowingnitrogen for 60 minutes. The pH of the solution was raised from 8.5 to10.5 by addition of 9.5 mL of 1M NaOH. The flask purged with flowingnitrogen and heated to 60° C. at which time Ammonium Persulfate (APS,Aldrich, 7.73 mL of a 10% solution in water, mg, 0.6% relative to totalmonomers) was added. The resultant was stirred 24 hrs at 60° C.

¹H-NMR & ³¹P-NMR were run on the crude reaction solutions. Total monomerconversion of 78% was observed with broad P polymer peaks at ˜18 to 23ppm from the phosphonate group and −6 to −10 from the phosphate bound tothe phosphonate group.

The polymer was purified by adding methanol aliquots over 15 minutes toa stirred solution containing 10% active polymer. A turbid solutionresulted and was transferred to a separatory funnel and allowed to standfor an additional 15 minutes to fully separate into a lower viscouspolymer rich syrup and an upper fluid layer. The lower polymer layer wascollected and the upper layer reprecipitated using an additional aliquotof methanol and following repeating the same procedure. All samples werethen dried under vacuum for two days with the final mass recorded in theTable 4 below.

TABLE 4 Fraction ml MeOH Dried Mass 1 150 38.6 2 100 11.0 3 50 6.4 4 503.1 5 100 4.2 6 150 4.0

In addition, approximately 50 ml of the remaining upper H₂O/MeOH layerwas concentrated under N₂ stream overnight at room temperature followedby drying for 24 hours under vacuum at room temperature yielding 2.5 gwhite solid. Size exclusion chromatography/gel permeation chromatography(SEC or GPC, 3-columns in series, Polymer Standards Service MCX1000A,MCX500A and MCX100A all 5 rpm, with guard column, 0.2M NaNO₃ mobilephase 1 mL/min) showed sequential decreases in molecular weight fromfraction 1 with the highest molecular weight and fraction 6 with thelowest. The GPC trace plot resulting from the polymer analysis isprovided as FIG. 5. Higher molecular weight is represented by a shorterretention time, while lower molecular weight has a higher retentiontime. The large peaks after 22.5 minutes represent non polymer speciessuch as residual monomers, and salt impurities in the sodium vinylsulfate solution.

Example 61 Additional Purification of Vinyl Phosphono-monoPhosphate(VPP) and Sodium Vinyl Sulfonate (SVS) Samples from Example 60

Additional purification was performed on fractions 1-3 and 4-6. A 15weight % polymer solution in water was created from the combinedfractions 1-3. To this was added a mass of methanol equal to 20% of themass of the entire water fraction of 60 minutes with stirring. Stirringwas stopped and the solution phase separated to give a viscous polymerrich lower layer. This fraction was collected and dried. This procedurewas repeated three additional times with an additional 10% methanolrelative to the starting mass of solution added each time. All sampleswere oven dried with the percent of original mass recorded in the tablebelow. Fractions 1-4 were 77-81% active with less than 0.5% phosphate,less than 0.2% vinyl phosphate or vinyl phosphono-phosphate, with nodetectable vinyl sulfonate.

TABLE 5 Fraction % MeOH % of Total 1 20% 73%  2 30% 14%  3 40% 5% 4 50%4% Residual 4%

A 20 weight percent polymer solution was created from the combinedfractions 4-6. To this solution was added a mass of methanol equal to60% of the total mass of the solution. The resulting precipitant wasdried under vacuum for two days. The recovered polymer mass was 93% ofthe initial, 83% active, with less than 0.5% phosphate, less than 0.1%vinyl sulfonate, and less than 0.1% vinyl phosphonate or vinylphosphonate.

The GPC trace plot of the resulting refractioned materials is shown inFIG. 6.

In addition to RI detection, light scattering was also performed. Whilethe low retention time samples provide good light scattering, higherretention samples do not. This phenomenon was independently confirmedwith a standalone light scattering instrument not attached to GPC. Lowmolecular weight fractions appear to cluster which manifests as highmolecular weight and high error after work up of light scattering signalinto molecular weight. For this reason, only the molecular weights ofthe less retained materials are given. For more retained fraction, thetrend of increasing calculated Mn and Mw continues with uncertaintiesapproaching 50%. Polymer with Mw of 60,000 Daltons was detected forRefrac 1-3-1. This corresponds to a polymer of between 250 and 450repeat units depending upon the composition of vinyl sulfonate and vinylphosphono-phosphate derived units.

TABLE 6 Mn Mw (kDa) Uncertainty (kDa) Uncertainty Fractions 1-3 4.42.50% 6.5 1.60% Refrac 1-3 - 1 5.6 1.10% 6.8 0.90% Refrac 1-3 - 2 3.54.30% 4.0 3.90% Refrac 1-3 - 3 4.0 7.50% 4.9 12.30% Refrac 1-3 - 4 4.67.60% 6.1 18.90%

Example 62 Identification of End Groups by Different AnalyticalTechniques

HNMR of the refractionated samples from example 61 showed broad polymerpeaks in the olefin region of 6.5-5 ppm. Integration of these peaksversus the non-olefin peaks from 4.0-1.0 ppm can be used to approximatehow many olefins are present. Olefin areas were divided by 2 assuming avinyl like group, while the non-olefins were divided by 3 assuming aCH₂—CHX where X is a P or S. From the composition of each fraction,calculated with an internal standard combined HNMR and PNMR, the Mn canbe approximated under the assumption that every olefin corresponds to aterminal group. The closeness of this calculation with the lightscattering (LS) result for Mn can then be used to gauge if each polymerhas an olefin at a terminal position. The comparative results are givenin Table 7.

TABLE 7 Mn-LS MW-LS Mn-HNMR (kDa) (kDa) (kDa) Fractions 1-3 4.4 6.5 3.5Refrac 1-3 - 1 5.6 6.8 6.8 Refrac 1-3 - 2 3.5 4 2.7 Refrac 1-3 - 3 4 4.92.3 Refrac 1-3 - 4 4.6 6.1 2.0 Refrac 1-3 - Residual — — 0.8 Fractions4-6 — — 1.3 Refrac 4-6 - 1 — — 1.4 Refrac 4-6 - Residual — — 1.2

For the less retained and presumably higher molecular weight species,the match is quite close, with values of 5.6 vs 6.8 and 3.5 vs. 2.7 forRefrac 1-3-1 and 2. Unlike light scattering, olefin based analysis alsoindicates that Mn does decrease with higher fractions that are moreretained on the columns. To confirm the CH₂ nature of the olefins,edited heteronuclear single quantum coherence (Edited-HSQC) NMR was runon sample Refrac 4-6-1. The olefin peaks were confirmed to be of CH₂character.

Sample Refrac 1-3-4 was also analyzed by ion chromatography (DionexIonPac AS 16-4 μm) followed by high resolution mass spectrometry. Inaddition to a large broad polymer peak with many signals, a sharp earlyeluting (less total charge) peak was also seen. This early eluting peakwas found to contain and match the multiple masses for a “trimer” ofphosphono-phosphate, including the proton form, sodium form, mixtures ofproton and sodium as well as masses corresponding to the loss or gain ofwater and loss of a phosphate group. This species was found to containan unsaturation, either olefinic or cyclic. Given the Edited-HSQCresult, the structure of the fully protonic form is shown.

It is assumed that other end groups besides olefins are also present. Inthe synthesis of the refractionated samples, 0.6% initiator relative tototal moles of polymerizable monomers was used. Typical initiatorefficiency is less than 100%, but for the sake of calculation this valuewill be used. Each persulfate can split to form 2 radicals. If eachradical starts a polymer chain and the reaction proceeds to completion,each chain is expected to have 83 repeat units. The initial combinedfraction 1-3 had an average of 19 repeat units while 4-6 had 6 repeatunits from the HNMR data. Therefore, assuming every initiator radicalperfectly initiated a polymer, a minimum of 4 chain transfers orbackbiting and beta scission combinations took place on that chain, witheach transfer likely producing an olefin. Assuming only 40% efficiencyof initiation, 208 repeat units is expected meaning 11 chain transfersor backbiting and beta scission combinations occurred from eachinitiator radical.

It is understood that the examples and embodiments described herein arefor illustrative purposes only and that various modifications or changesin light thereof will be suggested to one skilled in the art withoutdeparting from its spirit and scope.

The dimensions and values disclosed herein are not to be understood asbeing strictly limited to the exact numerical values recited. Instead,unless otherwise specified, each such dimension is intended to mean boththe recited value and a functionally equivalent range surrounding thatvalue. For example, a dimension disclosed as “40 mm” is intended to mean“about 40 mm.”

Every document cited herein, including any cross referenced or relatedpatent or application and any patent application or patent to which thisapplication claims priority or benefit thereof, is hereby incorporatedherein by reference in its entirety unless expressly excluded orotherwise limited. The citation of any document is not an admission thatit is prior art with respect to any invention disclosed or claimedherein or that it alone, or in any combination with any other referenceor references, teaches, suggests or discloses any such invention.Further, to the extent that any meaning or definition of a term in thisdocument conflicts with any meaning or definition of the same term in adocument incorporated by reference, the meaning or definition assignedto that term in this document shall govern.

While particular embodiments of the present invention have beenillustrated and described, it would be obvious to those skilled in theart that various other changes and modifications can be made withoutdeparting from the spirit and scope of the invention. It is thereforeintended to cover in the appended claims all such changes andmodifications that are within the scope of this invention.

What is claimed is:
 1. An oral care composition comprising a polymercomprising a phosphono-phosphate group and an anionic group wherein saidphosphono-phosphate group has the structure of Formula 1:

wherein: ε is the site of attachment to a carbon atom in the polymerbackbone, side group, or side chain; R₁ is selected from the groupconsisting of —H, alkyl, alkanediyl-alkoxy, metal salt having Na, K, Ca,Mg, Mn, Zn, Fe, or Sn cation, amine cation salt, and a structure ofFormula 2:

wherein: θ is the site of attachment to Formula 1, R₄ and R₅ areindependently selected from the group consisting of —H, alkyl,alkanediyl-alkoxy, metal salt having Na, K, Ca, Mg, Mn, Zn, Fe, or Sncation, and amine cation salt; R₂ is selected from the group consistingof —H, alkyl, alkanediyl-alkoxy, metal salt having Na, K, Ca, Mg, Mn,Zn, Fe, or Sn cation, amine cation salt, and a structure of Formula 3:

wherein: θ is the site of attachment to Formula 1, R₆, and R₇ areindependently selected from the group consisting of —H, alkyl,alkanediyl-alkoxy, metal salt having Na, K, Ca, Mg, Mn, Zn, Fe, or Sncation, and amine cation salt, and n is an integer from 1 to 22; and R₃is selected from the group consisting of —H, alkyl, alkanediyl-alkoxy,metal salt having Na, K, Ca, Mg, Mn, Zn, Fe, or Sn cation, and aminecation salt, wherein said anionic group is covalently bound to thepolymer backbone, side group, or side chain and is selected from thechemical group consisting of phosphate, phosphonate, phosphinate,sulfate, sulfonate, sulfinate, mercapto, carboxylate, hydroxyamino,amine oxide, and hydroxamate.
 2. The oral care composition of claim 1wherein the polymer is created using monomers and at least one monomerused to create said polymer comprises said phosphono-phosphate group. 3.The oral care composition of claim 1 wherein the polymer is createdusing monomers and at least one monomer used to create said polymercomprises said anionic group.
 4. The oral care composition of claim 1wherein the polymer is created using monomers and at least one monomerused to create said polymer comprises said anionic group and at leastone monomer used to create said polymer comprises saidphosphono-phosphate group.
 5. The oral care composition of claim 1wherein said phosphono-phosphate group is added during apost-polymerization modification.
 6. The oral care composition of claim2 wherein said at least one monomer has the structure of Formula 4

wherein: β is the site of attachment to the phosphono-phosphate group ofFormula 1; R₈ is selected from the group consisting of —H and —CH₃; L₁is selected from the group consisting of a chemical bond, arenediyl, anda structure of Formula 5:

wherein: α is the site of attachment to the alkenyl radical in Formula4; β is the site of attachment to the phosphono-phosphate group ofFormula 1; X is selected from the group consisting of the structures inFormulas 6-12;

wherein: R₉ is selected from the group consisting of —H, alkyl_((C1-8)),phosphonoalkyl, and phosphono(phosphate)alkyl; and Y is selected fromthe group consisting of alkanediyl, alkoxydiyl, alkylaminodiyl andalkenediyl.
 7. The oral care composition of claim 6 wherein L₁ is acovalent bond.
 8. The oral care composition of claim 6 wherein L₁ hasthe structure of Formula
 5. 9. The oral care composition of claim 8wherein the structure of X is selected from the group consisting ofFormula 6, Formula 9, and Formula
 11. 10. The oral care composition ofclaim 1 wherein said anionic group is selected from the group consistingof phosphate, phosphonate, sulfate, sulfonate, and carboxylate.
 11. Theoral care composition of claim 1 wherein said anionic group issulfonate.
 12. The oral care composition of claim 1 wherein said anionicgroup is carboxylate.
 13. The oral care composition of claim 1 whereinsaid anionic group is phosphonate.
 14. The oral care composition ofclaim 3 wherein said at least one monomer further comprises an alkenylgroup of the structure represented in Formula 13,

wherein: R₁₀ is selected from the group consisting of H or CH₃ and L₂ isa linking group to the anionic group.
 15. The oral care composition ofclaim 3 wherein said at least one monomer has the structure representedin Formula 14,

wherein: R₁₁ is selected from the group consisting of H and alkyl; δ isthe site of attachment to the anionic group; L₃ is selected from thegroup consisting of a chemical bond, arenediyl, and a structure ofFormula 15;

wherein: γ is the site of attachment to the alkenyl radical; δ is thesite of attachment to the anionic group; W is selected from thestructures in Formulas 16-22:

wherein: R₁₂ is selected from the group consisting of —H, andalkyl_((C1-8)), and V is selected from the group consisting ofalkanediyl, alkoxydiyl, alkylaminodiyl or alkenediyl.
 16. The oral carecomposition of claim 3 wherein said at least one monomer is selectedfrom the group consisting of vinyl phosphonate, vinyl sulfonate,acrylate, methyl vinyl phosphonate, methyl vinyl sulfonate,methacrylate, styrene phosphonate, styrene sulfonate, vinyl benzenephosphonate, vinyl benzene sulfonate, 2-acrylamido-2-methyl propanesulfonate (AMPS), and 2-Sulfopropyl Acrylate (SPA).
 17. The oral carecomposition of claim 4 wherein the ratio of said at least one monomercomprising said phosphono-phosphate group to said at least one monomercomprising said anionic group ranges from 99.9:0.1 to 0.1:99.9,respectively.
 18. The oral care composition of claim 4 wherein the ratioof said at least one monomer comprising said phosphono-phosphate groupto said at least one monomer comprising said anionic group ranges from99:1 to 1:99, respectively.
 19. The oral care composition of claim 4wherein the ratio of said at least one monomer comprising saidphosphono-phosphate group to said at least one monomer comprising saidanionic group ranges from 90:10 to 10:90, respectively.
 20. The oralcare composition of claim 4 wherein the ratio of said at least onemonomer comprising said phosphono-phosphate group to said at least onemonomer comprising said anionic group ranges from 70:30 to 30:70,respectively.
 21. The oral care composition of claim 1 wherein saidcomposition further comprises from about 5% to about 70%, by weight ofthe composition, of water.
 22. The oral care composition of claim 1wherein said composition further comprises from about 0.1% to about 11%,by weight of the composition, of a metal ion salt.
 23. The oral carecomposition of claim 22 wherein said metal ion salt is stannousfluoride.